@article {2024|2168, title = {The characterization of ancient Methanococcales malate dehydrogenases reveals that strong thermal stability prevents unfolding under intense γ-irradiation}, journal = {Mol. Biol. Evol.}, volume = {41}, year = {2024}, abstract = {

Malate dehydrogenases (MalDHs) (EC.1.1.1.37), which are involved in the conversion of oxaloacetate to pyruvate in the tricarboxylic acid cycle, are a relevant model for the study of enzyme evolution and adaptation. Likewise, a recent study showed that Methanococcales, a major lineage of Archaea, is a good model to study the molecular processes of proteome thermoadaptation in prokaryotes. Here, we use ancestral sequence reconstruction and paleoenzymology to characterize both ancient and extant MalDHs. We observe a good correlation between inferred optimal growth temperatures and experimental optimal temperatures for activity (A-Topt). In particular, we show that the MalDH present in the ancestor of Methanococcales was hyperthermostable and had an A-Topt of 80 \°C, consistent with a hyperthermophilic lifestyle. This ancestor gave rise to two lineages with different thermal constraints: one remained hyperthermophilic, while the other underwent several independent adaptations to colder environments. Surprisingly, the enzymes of the first lineage have retained a thermoresistant behavior (i.e. strong thermostability and high A-Topt), whereas the ancestor of the second lineage shows a strong thermostability, but a reduced A-Topt. Using mutants, we mimic the adaptation trajectory toward mesophily and show that it is possible to significantly reduce the A-Topt without altering the thermostability of the enzyme by introducing a few mutations. Finally, we reveal an unexpected link between thermostability and the ability to resist γ-irradiation-induced unfolding.

}, keywords = {ancestral sequence reconstruction, COaLA evolutionary model, extremophiles, irradiation, reactive oxygen species, thermal adaptation}, author = {Madern, Dominique and Halgand, Fr{\'e}d{\'e}ric and Hou{\'e}e-Levin, Chantal and Dufour, Anne-B{\'e}atrice and Coquille, Sandrine and Ansanay-Alex, Salom{\'e} and S Sacquin-Mora and Brochier-Armanet, C{\'e}line} } @article {2023, title = {Conformational and mechanical stability of the isolated large subunit of membrane-bound [NiFe]-hydrogenase from Cupriavidus necator}, journal = {Frontiers in Microbiology}, volume = {13}, year = {2023}, abstract = {

Comprising at least a bipartite architecture, the large subunit of [NiFe]-hydrogenase harbors the catalytic nickel\–iron site while the small subunit houses an array of electron-transferring Fe-S clusters. Recently, some [NiFe]-hydrogenase large subunits have been isolated showing an intact and redox active catalytic cofactor. In this computational study we have investigated one of these metalloproteins, namely the large subunit HoxG of the membrane-bound hydrogenase from Cupriavidus necator (CnMBH), targeting its conformational and mechanical stability using molecular modelling and long all-atom Gaussian accelerated molecular dynamics (GaMD). Our simulations predict that isolated HoxG is stable in aqueous solution and preserves a large portion of its mechanical properties, but loses rigidity in regions around the active site, in contrast to the MBH heterodimer. Inspired by biochemical data showing dimerization of the HoxG protein and IR measurements revealing an increased stability of the [NiFe] cofactor in protein preparations with higher dimer content, corresponding simulations of homodimeric forms were also undertaken. While the monomeric subunit contains several flexible regions, our data predicts a regained rigidity in homodimer models. Furthermore, we computed the electrostatic properties of models obtained by enhanced sampling with GaMD, which displays a significant amount of positive charge at the protein surface, especially in solvent-exposed former dimer interfaces. These data offer novel insights on the way the [NiFe] core is protected from de-assembly and provide hints for enzyme anchoring to surfaces, which is essential information for further investigations on these minimal enzymes.

}, issn = {1664-302X}, doi = {10.3389/fmicb.2022.1073315}, url = {https://www.frontiersin.org/articles/10.3389/fmicb.2022.1073315}, author = {Dragelj, Jovan and Karafoulidi-Retsou, Chara and Katz, Sagie and Lenz, Oliver and Zebger, Ingo and Caserta, Giorgio and S Sacquin-Mora and Mroginski, Maria Andrea} } @article {2022|2156, title = {Building Biological Relevance Into Integrative Modelling of Macromolecular Assemblies}, journal = {Frontiers in Molecular Biosciences}, volume = {9}, year = {2022}, pages = {826136}, abstract = {

Recent advances in structural biophysics and integrative modelling methods now allow us to decipher the structures of large macromolecular assemblies. Understanding the dynamics and mechanisms involved in their biological function requires rigorous integration of all available data. We have developed a complete modelling pipeline that includes analyses to extract biologically significant information by consistently combining automated and interactive human-guided steps. We illustrate this idea with two examples. First, we describe the ryanodine receptor, an ion channel that controls ion flux across the cell membrane through transitions between open and closed states. The conformational changes associated with the transitions are small compared to the considerable system size of the receptor; it is challenging to consistently track these states with the available cryo-EM structures. The second example involves homologous recombination, in which long filaments of a recombinase protein and DNA catalyse the exchange of homologous DNA strands to reliably repair DNA double-strand breaks. The nucleoprotein filament reaction intermediates in this process are short-lived and heterogeneous, making their structures particularly elusive. The pipeline we describe, which incorporates experimental and theoretical knowledge combined with state-of-the-art interactive and immersive modelling tools, can help overcome these challenges. In both examples, we point to new insights into biological processes that arise from such interdisciplinary approaches.

}, issn = {2296-889X}, doi = {10.3389/fmolb.2022.826136}, url = {https://www.frontiersin.org/article/10.3389/fmolb.2022.826136}, author = {Molza, Anne-Elisabeth and Westermaier, Yvonne and Moutte, Magali and Ducrot, Pierre and Danilowicz, Claudia and Godoy-Carter, Veronica and Prentiss, Mara and Robert, Charles H. and Marc Baaden and Pr{\'e}vost, Chantal} } @article {2022|2157, title = {Consistent Picture of Phosphate{\textendash}Divalent Cation Binding from Models with Implicit and Explicit Electronic Polarization}, journal = {J. Phys. Chem. B}, volume = {126}, year = {2022}, month = {05/2022}, pages = {4022-4034}, doi = {10.1021/acs.jpcb.2c01158}, url = {https://pubs.acs.org/doi/full/10.1021/acs.jpcb.2c01158}, author = {Julie Puyo-Fourtine and Marie Juill{\'e} and J{\'e}r{\^o}me H{\'e}nin and Carine Clavagu{\'e}ra and Elise Dubou{\'e}-Dijon} } @article {2022|2161, title = {Enhanced Sampling Methods for Molecular Dynamics Simulations [Article v1.0]}, journal = {Living Journal of Computational Molecular Science}, volume = {4}, year = {2022}, month = {Dec.}, pages = {1583}, abstract = {

Enhanced sampling algorithms have emerged as powerful methods to extend the utility of molecular dynamics simulations and allow the sampling of larger portions of the configuration space of complex systems in a given amount of simulation time. This review aims to present the unifying principles of and differences between many of the computational methods currently used for enhanced sampling in molecular simulations of biomolecules, soft matter and molecular crystals. In fact, despite the apparent abundance and divergence of such methods, the principles at their core can be boiled down to a relatively limited number of statistical and physical concepts. To enable comparisons, the various methods are introduced using similar terminology and notation. We then illustrate in which ways many different methods combine features of a relatively small number of the same enhanced sampling concepts. This review is intended for scientists with an understanding of the basics of molecular dynamics simulations and statistical physics who want a deeper understanding of the ideas that underlie various enhanced sampling methods and the relationships between them. This living review is intended to be updated to continue to reflect the wealth of sampling methods as they continue to emerge in the literature.

}, doi = {10.33011/livecoms.4.1.1583}, url = {https://livecomsjournal.org/index.php/livecoms/article/view/v4i1e1583}, author = {J{\'e}r{\^o}me H{\'e}nin and Leli{\`e}vre, Tony and Shirts, Michael R. and Valsson, Omar and Delemotte, Lucie} } @article {2022|2160, title = {Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation}, journal = {Nature Communications}, volume = {13}, year = {2022}, doi = {10.1038/s41467-022-34813-5}, url = {https://doi.org/10.1038/s41467-022-34813-5}, author = {John T. Petroff and Noah M. Dietzen and Ezry Santiago-McRae and Brett Deng and Maya S. Washington and Lawrence J. Chen and K. Trent Moreland and Zengqin Deng and Michael Rau and James A. J. Fitzpatrick and Peng Yuan and Thomas T. Joseph and J{\'e}r{\^o}me H{\'e}nin and Grace Brannigan and Wayland W. L. Cheng} } @article {2021|2148, title = {Building intuition for binding free energy calculations: Bound state definition, restraints, and symmetry}, journal = {The Journal of Chemical Physics}, volume = {154}, year = {2021}, pages = {204101}, doi = {10.1063/5.0046853}, url = {https://doi.org/10.1063/5.0046853}, author = {Elise Dubou{\'e}-Dijon and J{\'e}r{\^o}me H{\'e}nin} } @article {2021|2154, title = {Influences of ssDNA-RecA Filament Length on the Fidelity of Homologous Recombination}, journal = {Journal of Molecular Biology}, volume = {433}, year = {2021}, pages = {167143}, abstract = {

Chromosomal double-strand breaks can be accurately repaired by homologous recombination, but genomic rearrangement can result if the repair joins different copies of a repeated sequence. Rearrangement can be advantageous or fatal. During repair, a broken double-stranded DNA (dsDNA) is digested by the RecBCD complex from the 5 {\"A} end, leaving a sequence gap that separates two 3{\"A} single-stranded DNA (ssDNA) tails. RecA binds to the 3 {\"A} tails forming helical nucleoprotein filaments.A three-strand intermediate is formed when a RecA-bound ssDNA with L nucleotides invades a homologous region of dsDNA and forms a heteroduplex product with a length \≤ L bp. The homology dependent stability of the heteroduplex determines how rapidly and accurately homologous recombination repairs double-strand breaks. If the heteroduplex is sufficiently sequence matched, repair progresses to irreversible DNA synthesis. Otherwise, the heteroduplex should rapidly reverse. In this work, we present in vitro measurements of the L dependent stability of heteroduplex products formed by filaments with 90 \≤ L \≤ 420 nt, which is within the range observed in vivo. We find that without ATP hydrolysis, products are irreversible when L \> 50 nt. In contrast, with ATP hydrolysis when L \< 160 nt, products reverse in \< 30 seconds; however, with ATP hydrolysis when L \>= 320 nt, some products reverse in \< 30 seconds, while others last thousands of seconds. We consider why these two different filament length regimes show such distinct behaviors. We propose that the experimental results combined with theoretical insights suggest that filaments with 250 \≤ L \≤ 8500 nt optimize DSB repair.

}, keywords = {biased random walk, D-loop turnover, Double-strand break repair, genomic rearrangement, multiple reversible intermediates}, issn = {0022-2836}, doi = {https://doi.org/10.1016/j.jmb.2021.167143}, url = {https://www.sciencedirect.com/science/article/pii/S0022283621003727}, author = {Claudia Danilowicz and Evan Vietorisz and Veronica Godoy-Carter and Chantal Pr{\'e}vost and Mara Prentiss} } @article {2021|2147, title = {Mechanistic Insights on Heme-to-Heme Transmembrane Electron Transfer Within NADPH Oxydases From Atomistic Simulations.}, journal = {Front Chem}, volume = {9}, year = {2021}, month = {2021}, pages = {650651}, abstract = {

NOX5 is a member of the NADPH oxidase family which is dedicated to the production of reactive oxygen species. The molecular mechanisms governing transmembrane electron transfer (ET) that permits to shuttle electrons over the biological membrane have remained elusive for a long time. Using computer simulations, we report conformational dynamics of NOX5 embedded within a realistic membrane environment. We assess the stability of the protein within the membrane and monitor the existence of cavities that could accommodate dioxygen molecules. We investigate the heme-to-heme electron transfer. We find a reaction free energy of a few tenths of eV (ca. -0.3 eV) and a reorganization free energy of around 1.1 eV (0.8 eV after including electrostatic induction corrections). The former indicates thermodynamically favorable ET, while the latter falls in the expected values for transmembrane inter-heme ET. We estimate the electronic coupling to fall in the range of the μeV. We identify electron tunneling pathways showing that not only the W378 residue is playing a central role, but also F348. Finally, we reveal the existence of two connected Obinding pockets near the outer heme with fast exchange between the two sites on the nanosecond timescale. We show that when the terminal heme is reduced, O binds closer to it, affording a more efficient tunneling pathway than when the terminal heme is oxidized, thereby providing an efficient mechanism to catalyze superoxide production in the final step. Overall, our study reveals some key molecular mechanisms permitting reactive oxygen species production by NOX5 and paves the road for further investigation of ET processes in the wide family of NADPH oxidases by computer simulations.

}, issn = {2296-2646}, doi = {10.3389/fchem.2021.650651}, author = {Wu, Xiaojing and J{\'e}r{\^o}me H{\'e}nin and Baciou, Laura and Marc Baaden and Cailliez, Fabien and de la Lande, Aur{\'e}lien} } @article {2020|2117, title = {Aggregation of disease-related peptides.}, journal = {Prog Mol Biol Transl Sci}, volume = {170}, year = {2020}, month = {2020}, pages = {435-460}, abstract = {

Protein misfolding and aggregation of amyloid proteins is the fundamental cause of more than 20 diseases. Molecular mechanisms of the self-assembly and the formation of the toxic aggregates are still elusive. Computer simulations have been intensively used to study the aggregation of amyloid peptides of various amino acid lengths related to neurodegenerative diseases. We review atomistic and coarse-grained simulations of short amyloid peptides aimed at determining their transient oligomeric structures and the early and late aggregation steps.

}, issn = {1878-0814}, doi = {10.1016/bs.pmbts.2019.12.002}, author = {Phuong Hoang Nguyen and Sterpone, Fabio and Philippe Derreumaux} } @article {2020|2145, title = {Binding of divalent cations to acetate: molecular simulations guided by Raman spectroscopy}, journal = {Phys. Chem. Chem. Phys.}, volume = {22}, year = {2020}, pages = {24014-24027}, chapter = {24014}, abstract = {

In spite of the biological importance of the binding of Zn2+, Ca2+, and Mg2+ to the carboxylate group, cation\–acetate binding affinities and binding modes remain actively debated. Here, we report the first use of Raman multivariate curve resolution (Raman-MCR) vibrational spectroscopy to obtain self-consistent free and bound metal acetate spectra and one-to-one binding constants, without the need to invoke any a priori assumptions regarding the shapes of the corresponding vibrational bands. The experimental results, combined with classical molecular dynamics simulations with a force field effectively accounting for electronic polarization via charge scaling and ab initio simulations, indicate that the measured binding constants pertain to direct (as opposed to water separated) ion pairing. The resulting binding constants do not scale with cation size, as the binding constant to Zn2+ is significantly larger than that to either Mg2+ or Ca2+, although Zn2+ and Mg2+ have similar radii that are about 25\% smaller than Ca2+. Remaining uncertainties in the metal acetate binding free energies are linked to fundamental ambiguities associated with identifying the range of structures pertaining to non-covalently bound species.

}, doi = {10.1039/D0CP02987D}, url = {https://pubs.rsc.org/en/content/articlelanding/2020/cp/d0cp02987d$\#$!divAbstract}, author = {Mendes de Oliveira, Denilson and Samual R. Zukowski and Vladimir Palivec and J{\'e}r{\^o}me H{\'e}nin and Hector Martinez-Seara and Dor Ben-Amotz and Pavel Jungwirth and Elise Dubou{\'e}-Dijon} } @article {2020|2126, title = {Impact of A2T and D23N Mutations on Tetrameric Aβ42 Barrel within a Dipalmitoylphosphatidylcholine Lipid Bilayer Membrane by Replica Exchange Molecular Dynamics.}, journal = {J Phys Chem B}, volume = {124}, year = {2020}, month = {2020 Feb 20}, pages = {1175-1182}, abstract = {

In Alzheimer\&$\#$39;s disease (AD), many experimental and computational studies support the amyloid pore hypothesis of the Aβ42 peptide. We recently designed a β-barrel tetramer in a membrane-mimicking environment consistent with some low-resolution experimental data. In this earlier study, by using extensive replica exchange molecular dynamics simulations, we found that the wild-type (WT) Aβ42 peptides have a high propensity to form β-barrels, while the WT Aβ40 peptides do not. In this work, we have investigated the effect of mutations D23N and A2T on the Aβ42 barrel tetramer by using the same enhanced conformational sampling technique. It is known that the D23N mutation leads to early onset AD, while the A2T mutation protects from AD. This computational study in a dipalmitoylphosphatidylcholine (DPPC) lipid bilayer membrane shows that the WT sequence and its A2T variant have similar β-barrel populations and the three-dimensional model is slightly destabilized for D23N compared to its WT sequence. These extensive modeling calculations indicate that the lower and higher induced toxicity of these two mutations in AD cannot be correlated to their β-barrel tetramer stabilities in a DPPC lipid bilayer membrane.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.9b11881}, author = {Ngo, Son Tung and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2020|2125, title = {Impact of the Astaxanthin, Betanin, and EGCG Compounds on Small Oligomers of Amyloid Aβ Peptide.}, journal = {J Chem Inf Model}, volume = {60}, year = {2020}, month = {2020 Mar 23}, pages = {1399-1408}, abstract = {

There is experimental evidence that the astaxanthin, betanin, and epigallocatechin-3-gallate (EGCG) compounds slow down the aggregation kinetics and the toxicity of the amyloid-β (Aβ) peptide. How these inhibitors affect the self-assembly at the atomic level remains elusive. To address this issue, we have performed for each ligand atomistic replica exchange molecular dynamic (REMD) simulations in an explicit solvent of the Aβ trimer from the U-shape conformation and MD simulations starting from Aβ dimer and tetramer structures characterized by different intra- and interpeptide conformations. We find that the three ligands have similar binding free energies on small Aβ oligomers but very distinct transient binding sites that will affect the aggregation of larger assemblies and fibril elongation of the Aβ peptide.

}, issn = {1549-960X}, doi = {10.1021/acs.jcim.9b01074}, author = {Minh Hung, Huynh and Nguyen, Minh Tho and Tran, Phuong-Thao and Truong, Vi Khanh and Chapman, James and Quynh Anh, Le Huu and Philippe Derreumaux and Vu, Van V and Ngo, Son Tung} } @article {2020|2143, title = {A practical guide to biologically relevant molecular simulations with charge scaling for electronic polarization.}, journal = {J Chem Phys}, volume = {153}, year = {2020}, month = {2020 Aug 07}, pages = {050901}, abstract = {

Molecular simulations can elucidate atomistic-level mechanisms of key biological processes, which are often hardly accessible to experiment. However, the results of the simulations can only be as trustworthy as the underlying simulation model. In many of these processes, interactions between charged moieties play a critical role. Current empirical force fields tend to overestimate such interactions, often in a dramatic way, when polyvalent ions are involved. The source of this shortcoming is the missing electronic polarization in these models. Given the importance of such biomolecular systems, there is great interest in fixing this deficiency in a computationally inexpensive way without employing explicitly polarizable force fields. Here, we review the electronic continuum correction approach, which accounts for electronic polarization in a mean-field way, focusing on its charge scaling variant. We show that by pragmatically scaling only the charged molecular groups, we qualitatively improve the charge-charge interactions without extra computational costs and benefit from decades of force field development on biomolecular force fields.

}, issn = {1089-7690}, doi = {10.1063/5.0017775}, author = {Dubou{\'e}-Dijon, E and Javanainen, M and Delcroix, P and Jungwirth, P and Martinez-Seara, H} } @article {2020|2116, title = {Stability of Aβ11-40 Trimers with Parallel and Antiparallel β-Sheet Organizations in a Membrane-Mimicking Environment by Replica Exchange Molecular Dynamics Simulation}, journal = {The Journal of Physical Chemistry B}, year = {2020}, author = {Ngo, Son Tung and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2020|2140, title = {Structural transitions in the RNA 7SK 5{\textquoteright} hairpin and their effect on HEXIM binding}, journal = {Nucleic Acids Res}, volume = {48}, year = {2020}, month = {01}, pages = {373-389}, abstract = {

7SK RNA, as part of the 7SK ribonucleoprotein complex, is crucial to the regulation of transcription by RNA-polymerase II, via its interaction with the positive transcription elongation factor P-TEFb. The interaction is induced by binding of the protein HEXIM to the 5\&$\#$39; hairpin (HP1) of 7SK RNA. Four distinct structural models have been obtained experimentally for HP1. Here, we employ computational methods to investigate the relative stability of these structures, transitions between them, and the effects of mutations on the observed structural ensembles. We further analyse the results with respect to mutational binding assays, and hypothesize a mechanism for HEXIM binding. Our results indicate that the dominant structure in the wild type exhibits a triplet involving the unpaired nucleotide U40 and the base pair A43-U66 in the GAUC/GAUC repeat. This conformation leads to an open major groove with enough potential binding sites for peptide recognition. Sequence mutations of the RNA change the relative stability of the different structural ensembles. Binding affinity is consequently lost if these changes alter the dominant structure.

}, doi = {10.1093/nar/gkz1071}, author = {R{\"o}der, Konstantin and Guillaume Stirnemann and Dock-Bregeon, Anne-Catherine and Wales, David J and Pasquali, Samuela} } @article {2020|2131, title = {Tau R3-R4 Domain Dimer of the Wild Type and Phosphorylated Ser356 Sequences. I. In Solution by Atomistic Simulations.}, journal = {J Phys Chem B}, year = {2020}, month = {2020 Mar 27}, abstract = {

In Alzheimer\&$\#$39;s disease, neurofibrillary lesions correlate with cognitive deficits and consist of inclusions of tau protein with cross-β structure. A stable dimeric form of soluble tau has been evidenced in the cells, but its high-resolution structure is missing in solution. We know, however, that cryo-electron microscopy (c-EM) of full-length tau in the brain of an individual with AD displays a core of eight β-sheets with a C-shaped architecture spanning the R3-R4 repeat domain, while the rest of the protein is very flexible. To address the conformational ensemble of the dimer, we performed atomistic replica exchange molecular dynamics simulations on the tau R3-R4 domain starting from the c-EM configuration. We find that the wild type tau R3-R4 dimer explores elongated, U-shaped, V-shaped and globular forms rather than the C-shape. Phosphorylation of Ser356, pSer356, is known to block the interaction between the tau protein and the amyloid-β42 peptide. Standard molecular dynamics simulations of this phosphorylated sequence for a total of 5 microseconds compared to its wild type counterpart show a modulation of the population of β-helices and accessible topologies, and a decrease of intermediates near the fibril like conformers.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.0c00574}, author = {Philippe Derreumaux and Man, Viet Hoang and Wang, Junmei and Phuong Hoang Nguyen} } @article {2019|2109, title = {Amyloid-β (29{\textendash}42) Dimeric Conformations in Membranes Rich in Omega-3 and Omega-6 Polyunsaturated Fatty Acids}, journal = {The Journal of Physical Chemistry B}, volume = {123}, year = {2019}, pages = {2687{\textendash}2696}, author = {Lu, Yan and Shi, Xiao-Feng and Phuong Hoang Nguyen and Sterpone, Fabio and Salsbury Jr, Freddie R and Philippe Derreumaux} } @article {2019|2127, title = {C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ Tetramer in Solution: Intensive MD Study.}, journal = {ACS Omega}, volume = {4}, year = {2019}, month = {2019 Jun 30}, pages = {11066-11073}, abstract = {

Amyloid beta (Aβ) peptides are characterized as the major factors associated with neuron death in Alzheimer\&$\#$39;s disease, which is listed as the most common form of neurodegeneration. Disordered Aβ peptides are released from proteolysis of the amyloid precursor protein. The Aβ self-assembly process roughly takes place via five steps: disordered forms \→ oligomers \→ photofibrils \→ mature fibrils \→ plaques. Although Aβ fibrils are often observed in patient brains, oligomers were recently indicated to be major neurotoxic elements. In this work, the neurotoxic compound S-shape Aβ tetramer (S4Aβ) was investigated over 10 μs of unbiased MD simulations. In particular, the S4Aβ oligomer adopted a high dynamics structure, resulting in unsuccessful determination of their structures in experiments. The C-terminal was suggested as the possible nucleation of the Aβ aggregation. The sequences 27-35 and 39-40 formed rich β-content, whereas other residues mostly adopted coil structures. The mean value of the β-content over the equilibrium interval is \∼42 \± 3\%. Furthermore, the dissociation free energy of the S4Aβ peptide was predicted using a biased sampling method. The obtained free energy is Δ = -58.44 kcal/mol which is roughly the same level as the corresponding value of the U-shape Aβ peptide. We anticipate that the obtained S4Aβ structures could be used as targets for AD inhibitor screening over the in silico study.

}, issn = {2470-1343}, doi = {10.1021/acsomega.9b00992}, author = {Tung, Nguyen Thanh and Philippe Derreumaux and Vu, Van V and Nam, Pham Cam and Ngo, Son Tung} } @article {2019|2070, title = {Design games and game design: Relations between design, codesign and serious games in adult education}, journal = {From UXD to LivXD: Living eXperience Design}, year = {2019}, pages = {229{\textendash}253}, author = {Alvarez, Julian and Irrmann, Olivier and Djaouti, Damien and Antoine Taly and Rampnoux, Olivier and Sauv{\'e}, Louise} } @article {2019|2110, title = {Effects of all-atom molecular mechanics force fields on amyloid peptide assembly: the case of aβ16{\textendash}22 dimer}, journal = {Journal of chemical theory and computation}, volume = {15}, year = {2019}, pages = {1440{\textendash}1452}, author = {Man, Viet Hoang and He, Xibing and Philippe Derreumaux and Ji, Beihong and Xie, Xiang-Qun and Phuong Hoang Nguyen and Wang, Junmei} } @article {2019|2108, title = {Interaction mechanism between the focused ultrasound and lipid membrane at the molecular level}, journal = {The Journal of chemical physics}, volume = {150}, year = {2019}, pages = {215101}, author = {Man, Viet Hoang and Li, Mai Suan and Wang, Junmei and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2019|2067, title = {An inter-dimer allosteric switch controls NMDA receptor activity}, journal = {The EMBO journal}, volume = {38}, year = {2019}, author = {Esmenjaud, Jean-Baptiste and Stroebel, David and Chan, Kelvin and Grand, Teddy and David, M{\'e}lissa and Wollmuth, Lonnie P and Antoine Taly and Paoletti, Pierre} } @article {2019|2118, title = {Mesoscale biosimulations within a unified framework: from proteins to plasmids}, year = {2019}, pages = {1-12}, author = {P. Maiocchi and Philippe Derreumaux and F. Sterpone and S. Melchionna} } @article {2019|2122, title = {Modelling lipid systems in fluid with Lattice Boltzmann Molecular Dynamics simulations and hydrodynamics}, journal = {Scientific Reports}, volume = {9}, year = {2019}, pages = {16450}, abstract = {

In this work we present the coupling between Dry Martini, an efficient implicit solvent coarse-grained model for lipids, and the Lattice Boltzmann Molecular Dynamics (LBMD) simulation technique in order to include naturally hydrodynamic interactions in implicit solvent simulations of lipid systems. After validating the implementation of the model, we explored several systems where the action of a perturbing fluid plays an important role. Namely, we investigated the role of an external shear flow on the dynamics of a vesicle, the dynamics of substrate release under shear, and inquired the dynamics of proteins and substrates confined inside the core of a vesicle. Our methodology enables future exploration of a large variety of biological entities and processes involving lipid systems at the mesoscopic scale where hydrodynamics plays an essential role, e.g. by modulating the migration of proteins in the proximity of membranes, the dynamics of vesicle-based drug delivery systems, or, more generally, the behaviour of proteins in cellular compartments.

}, isbn = {2045-2322}, doi = {10.1038/s41598-019-52760-y}, url = {https://doi.org/10.1038/s41598-019-52760-y}, author = {F. Brandner, Astrid and Timr, Stepan and Melchionna, Simone and Philippe Derreumaux and Marc Baaden and Sterpone, Fabio} } @article {2019|2073, title = {A molecular perspective on mitochondrial membrane fusion: from the key players to oligomerization and tethering of mitofusin}, journal = {The Journal of membrane biology}, volume = {252}, year = {2019}, pages = {293{\textendash}306}, author = {De Vecchis, Dario and Brandner, Astrid and Marc Baaden and Cohen, Micka{\"e}l M and Antoine Taly} } @article {2019|2120, title = {Multiscale Aggregation of the Amyloid Aβ16{\textendash}22 Peptide: From Disordered Coagulation and Lateral Branching to Amorphous Prefibrils}, journal = {The Journal of Physical Chemistry Letters}, volume = {10}, year = {2019}, pages = {1594-1599}, doi = {10.1021/acs.jpclett.9b00423}, url = {https://doi.org/10.1021/acs.jpclett.9b00423}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Sterpone, Fabio} } @article {2019|2107, title = {Nonequilibrium atomistic molecular dynamics simulation of tubular nanomotor propelled by bubble propulsion}, journal = {The Journal of chemical physics}, volume = {151}, year = {2019}, pages = {024103}, author = {Man, Viet Hoang and Li, Mai Suan and Wang, Junmei and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2019|2121, title = {OPEP6: A New Constant-pH Molecular Dynamics Simulation Scheme with OPEP Coarse-Grained Force Field}, journal = {Journal of Chemical Theory and Computation}, volume = {15}, year = {2019}, pages = {3875-3888}, doi = {10.1021/acs.jctc.9b00202}, url = {https://doi.org/10.1021/acs.jctc.9b00202}, author = {Barroso da Silva, Fernando Luis and Sterpone, Fabio and Philippe Derreumaux} } @article {2019|2072, title = {Physics-based oligomeric models of the yeast mitofusin Fzo1 at the molecular scale in the context of membrane docking}, journal = {Mitochondrion}, volume = {49}, year = {2019}, pages = {234{\textendash}244}, author = {Brandner, Astrid and De Vecchis, Dario and Marc Baaden and Cohen, Micka{\"e}l M and Antoine Taly} } @article {2019|2062, title = {The positioning of Chi sites allows the RecBCD pathway to suppress some genomic rearrangements}, journal = {Nucleic Acids Res}, volume = {47}, year = {2019}, month = {02}, pages = {1836-1846}, abstract = {

Bacterial recombinational repair of double-strand breaks often begins with creation of initiating 3\&$\#$39; single-stranded DNA (ssDNA) tails on each side of a double-strand break (DSB). Importantly, if the RecBCD pathway is followed, RecBCD creates a gap between the sequences at 3\&$\#$39; ends of the initiating strands. The gap flanks the DSB and extends at least to the nearest Chi site on each strand. Once the initiating strands form ssDNA-RecA filaments, each ssDNA-RecA filament searches for homologous double-stranded DNA (dsDNA) to use as a template for the DNA synthesis needed to fill the gap created by RecBCD. Our experimental results show that the DNA synthesis requires formation of a heteroduplex dsDNA that pairs \>20 contiguous bases in the initiating strand with sequence matched bases in a strand from the original dsDNA. To trigger synthesis, the heteroduplex must be near the 3\&$\#$39; end of the initiating strand. Those experimentally determined requirements for synthesis combined with the Chi site dependence of the function of RecBCD and the distribution of Chi sites in bacterial genomes could allow the RecBCD pathway to avoid some genomic rearrangements arising from directly induced DSBs; however, the same three factors could promote other rearrangements.

}, doi = {10.1093/nar/gky1252}, author = {Li, Chastity and Danilowicz, Claudia and Tashjian, Tommy F and Godoy, Veronica G and Chantal Pr{\'e}vost and Prentiss, Mara} } @article {2019|2128, title = {Probable Transmembrane Amyloid α-Helix Bundles Capable of Conducting Ca Ions.}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {2019 Mar 28}, pages = {2645-2653}, abstract = {

Amyloid β (Aβ) peptides are considered the major causative agents of Alzheimer\&$\#$39;s disease (AD). In a widely accepted mechanism for AD pathogenesis, Aβ peptides are proposed to play multiple roles in damaging brain cells and their synaptic communications. Due to the heterogeneous nature of Aβ oligomers, their in vivo structures have not been understood. Most experimental and computational studies favored β-rich structures of Aβ as observed in Aβ fibrils. In this in silico study, we investigated an alternative perspective on the structures and function of Aβ oligomers in the cell membrane. Transmembrane α-helix bundles of the Aβ tetramer and trimer were observed in extensive temperature replica exchange molecular dynamics (REMD) simulations. We observed three minima on the free-energy landscape of each oligomer, namely, A, B, and C for the tetramer and D, E, and F for the trimer. Except for F, the minima consist of 4 or 3 parallel helices spanning across the membrane model dipalmitoylphosphatidylcholine. Replica exchange molecular dynamics-umbrella sampling (REMD-US) simulation was applied to study the process of a Ca crossing the pore formed by the α-helix bundles in A-E in comparison to that in a calcium channel and a proton channel. REMD-US reveals that A, C, and D allow Ca to cross their pore with a free-energy barrier comparable to that found for the calcium channel. In contrast, the free-energy barrier of a Ca ion crossing B, E, and the proton channel is significantly higher. This result suggests that Aβ peptide oligomers could form transmembrane α-helix bundles that provide feasible pathways for Ca transport. This is an intriguing observation that will stimulate further studies.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.8b10792}, author = {Ngo, Son Tung and Philippe Derreumaux and Vu, Van V} } @article {2019, title = {Quantifying the Strength of a Salt Bridge by Neutron Scattering and Molecular Dynamics}, journal = {J. Phys. Chem. Lett.}, volume = {10}, year = {2019}, chapter = {3254}, doi = {10.1021/acs.jpclett.9b01309}, url = {https://pubs.acs.org/doi/10.1021/acs.jpclett.9b01309}, author = {P.E. Mason and P. Jungwirth and Elise Dubou{\'e}-Dijon} } @article {2019|2063, title = {Residues in the fingers domain of the translesion DNA polymerase DinB enable its unique participation in error-prone double-strand break repair}, journal = {J Biol Chem}, volume = {294}, year = {2019}, month = {May}, pages = {7588-7600}, abstract = {

The evolutionarily conserved Escherichia coli translesion DNA polymerase IV (DinB) is one of three enzymes that can bypass potentially deadly DNA lesions on the template strand during DNA replication. Remarkably, however, DinB is the only known translesion DNA polymerase active in RecA-mediated strand exchange during error-prone double-strand break repair. In this process, a single-stranded DNA (ssDNA)-RecA nucleoprotein filament invades homologous dsDNA, pairing the ssDNA with the complementary strand in the dsDNA. When exchange reaches the 3\&$\#$39; end of the ssDNA, a DNA polymerase can add nucleotides onto the end, using one strand of dsDNA as a template and displacing the other. It is unknown what makes DinB uniquely capable of participating in this reaction. To explore this topic, we performed molecular modeling of DinB\&$\#$39;s interactions with the RecA filament during strand exchange, identifying key contacts made with residues in the DinB fingers domain. These residues are highly conserved in DinB, but not in other translesion DNA polymerases. Using a novel FRET-based assay, we found that DinB variants with mutations in these conserved residues are less effective at stabilizing RecA-mediated strand exchange than native DinB. Furthermore, these variants are specifically deficient in strand displacement in the absence of RecA filament. We propose that the amino acid patch of highly conserved residues in DinB-like proteins provides a mechanistic explanation for DinB\&$\#$39;s function in strand exchange and improves our understanding of recombination by providing evidence that RecA plays a role in facilitating DinB\&$\#$39;s activity during strand exchange.

}, keywords = {DinB, DNA damage, DNA polymerase, DNA polymerase IV, DNA repair, DNA synthesis, homologous recombination, RecA}, doi = {10.1074/jbc.RA118.006233}, author = {Tashjian, Tommy F and Danilowicz, Claudia and Molza, Anne-Elizabeth and Nguyen, Brian H and Chantal Pr{\'e}vost and Prentiss, Mara and Godoy, Veronica G} } @article {2019|2064, title = {Slow extension of the invading DNA strand in a D-loop formed by RecA-mediated homologous recombination may enhance recognition of DNA homology}, journal = {J Biol Chem}, volume = {294}, year = {2019}, month = {May}, pages = {8606-8616}, abstract = {

DNA recombination resulting from RecA-mediated strand exchange aided by RecBCD proteins often enables accurate repair of DNA double-strand breaks. However, the process of recombinational repair between short DNA regions of accidental similarity can lead to fatal genomic rearrangements. Previous studies have probed how effectively RecA discriminates against interactions involving a short similar sequence that is embedded in otherwise dissimilar sequences but have not yielded fully conclusive results. Here, we present results of in vitro experiments with fluorescent probes strategically located on the interacting DNA fragments used for recombination. Our findings suggest that DNA synthesis increases the stability of the recombination products. Fluorescence measurements can also probe the homology dependence of the extension of invading DNA strands in D-loops formed by RecA-mediated strand exchange. We examined the slow extension of the invading strand in a D-loop by DNA polymerase (Pol) IV and the more rapid extension by DNA polymerase LF-Bsu We found that when DNA Pol IV extends the invading strand in a D-loop formed by RecA-mediated strand exchange, the extension afforded by 82 bp of homology is significantly longer than the extension on 50 bp of homology. In contrast, the extension of the invading strand in D-loops by DNA LF-Bsu Pol is similar for intermediates with \≥50 bp of homology. These results suggest that fatal genomic rearrangements due to the recombination of small regions of accidental homology may be reduced if RecA-mediated strand exchange is immediately followed by DNA synthesis by a slow polymerase.

}, keywords = {cooperativity, DNA damage, DNA polymerase, DNA recombination, double-strand break (DSB), fluorescence resonance energy transfer (FRET), heteroduplex formation, molecular dynamics, RecA, strand displacement synthesis}, doi = {10.1074/jbc.RA119.007554}, author = {Lu, Daniel and Danilowicz, Claudia and Tashjian, Tommy F and Chantal Pr{\'e}vost and Godoy, Veronica G and Prentiss, Mara} } @article {2019|2078, title = {Structural dataset from microsecond-long simulations of yeast mitofusin Fzo1 in the context of membrane docking.}, journal = {Data Brief}, volume = {26}, year = {2019}, month = {2019 Oct}, pages = {104460}, abstract = {

In this work we present a novel set of possible auto-oligomerisation states of yeast protein Fzo1 in the context of membrane docking. The dataset reports atomistic models and trajectories derived from a molecular dynamics study of the yeast mitofusin Fzo1, residues 101-855. The initial modelling was followed by coarse-grained molecular dynamics simulation to evaluate the stability and the dynamics of each structural model in a solvated membrane environment. Simulations were run for 1\ μs and collected with GROMACS v5.0.4 using the martini v2.1 force field. For each structural model, the dataset comprises the production phase under semi-isotropic condition at 1\ bar, 310 K and 150 mn NaCl. The integration step is 20 fs and coordinates have been saved every 1 ns. Each trajectory is associated with a ready-available visualization state for the VMD software. These structural detailed informations are a ready-available platform to plan integrative studies on the mitofusin Fzo1 and will aid the community to further elucidate the mitochondrial tethering process during membrane fusion. This dataset is based on the publication \"Physics-based oligomeric models of the yeast mitofusin Fzo1 at the molecular scale in the context of membrane docking.\" (Brandner and De Vecchis et\ al., 2019)\".

}, issn = {2352-3409}, doi = {10.1016/j.dib.2019.104460}, author = {Brandner, Astrid and De Vecchis, Dario and Marc Baaden and Cohen, Micka{\"e}l M and Antoine Taly} } @article {2019|2106, title = {Tetrameric Aβ40 and Aβ42 β-Barrel Structures by Extensive Atomistic Simulations. I. In a Bilayer Mimicking a Neuronal Membrane.}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {2019 May 02}, pages = {3643-3648}, abstract = {

The amyloid-β (Aβ) 42 oligomers are much more toxic than Aβ40 oligomers in Alzheimer\&$\#$39;s disease. Numerous experiments indicate that toxicity could involve the formation of pores in membranes, but experimental high-resolution structure determination of these pore-forming Aβ oligomers has been impeded by aggregate heterogeneity. Using extensive atomistic simulations, low-resolution data obtained in lipid bilayers, and other theoretical factors, we proposed atomic structures of Aβ40 and Aβ42 β-barrels in a bilayer mimicking a neuronal membrane. The 3D model, which consists of tetramer subunits, two distinct β-hairpin motifs and an asymmetric arrangement of eight antiparallel β-strands, is drastically destabilized for Aβ40 compared to its Aβ42 counterpart. Our computational modeling has several implications in Alzheimer\&$\#$39;s disease, sheds light on the amyloid pore hypothesis, and explains the higher deleterious property of Aβ42.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.9b01206}, author = {Phuong Hoang Nguyen and Campanera, Josep M and Ngo, Son Tung and Loquet, Antoine and Philippe Derreumaux} } @article {2019|2105, title = {Tetrameric Aβ40 and Aβ42 β-Barrel Structures by Extensive Atomistic Simulations. II. In Aqueous Solution.}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {2019 Aug 08}, pages = {6750-6756}, abstract = {

Alzheimer\&$\#$39;s disease (AD) is characterized by the accumulation of extracellular Aβ42 and Aβ40 oligomers and plaques. In a recent computational study, we found that the presence of the residues I41 and A42 increases significantly the propensity of Aβ to form a tetrameric β-barrel structure in a bilayer mimicking a neuronal membrane. In this work, we have determined the propensity of the two Aβ proteins to form tetrameric β-barrel structures in aqueous solution using four atomistic protein fields, that is, Amber99SB-ILDN/TIP3P, OPLS/TIP3P, CHARMM36m/TIP3P-modified, and Amber99SB/DISP. Extensive replica exchange molecular dynamics simulations make it clear that a β-barrel, made of two distinct β-hairpin motifs and an asymmetric arrangement of eight antiparallel β-strands with an inner pore diameter of 0.7 nm, exists transiently for Aβ42 peptide, but this is less the case for Aβ40 peptide, due to the change of the CHC-CHC and the Cter-Cter interfaces. This study has several implications in AD.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.9b05288}, author = {Phuong Hoang Nguyen and Campanera, Josep M and Ngo, Son Tung and Loquet, Antoine and Philippe Derreumaux} } @article {2019|2065, title = {Weaving DNA strands: structural insight on ATP hydrolysis in RecA-induced homologous recombination}, journal = {Nucleic Acids Res}, volume = {47}, year = {2019}, month = {Sep}, pages = {7798-7808}, abstract = {

Homologous recombination is a fundamental process in all living organisms that allows the faithful repair of DNA double strand breaks, through the exchange of DNA strands between homologous regions of the genome. Results of three decades of investigation and recent fruitful observations have unveiled key elements of the reaction mechanism, which proceeds along nucleofilaments of recombinase proteins of the RecA family. Yet, one essential aspect of homologous recombination has largely been overlooked when deciphering the mechanism: while ATP is hydrolyzed in large quantity during the process, how exactly hydrolysis influences the DNA strand exchange reaction at the structural level remains to be elucidated. In this study, we build on a previous geometrical approach that studied the RecA filament variability without bound DNA to examine the putative implication of ATP hydrolysis on the structure, position, and interactions of up to three DNA strands within the RecA nucleofilament. Simulation results on modeled intermediates in the ATP cycle bring important clues about how local distortions in the DNA strand geometries resulting from ATP hydrolysis can aid sequence recognition by promoting local melting of already formed DNA heteroduplex and transient reverse strand exchange in a weaving type of mechanism.

}, doi = {10.1093/nar/gkz667}, author = {Boyer, Benjamin and Danilowicz, Claudia and Prentiss, Mara and Chantal Pr{\'e}vost} } @article {2018|2113, title = {Amyloid-β/drug interactions from computer simulations and cell-based assays}, journal = {Journal of Alzheimer{\textquoteright}s Disease}, volume = {64}, year = {2018}, pages = {S659{\textendash}S672}, author = {Phuong Hoang Nguyen and Del Castillo-Frias, Maria P and Berthoumieux, Olivia and Faller, Peter and Doig, Andrew J and Philippe Derreumaux} } @inbook {2018|2085, title = {Applications to water transport systems: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {389-414}, issn = {1364-5498}, doi = {10.1039/c8fd90022a}, author = {Marc Baaden and Barboiu, Mihail and Borthakur, Manash Pratim and Chen, Chun-Long and Coalson, Rob and Davis, Jeffery and Freger, Viatcheslav and Gong, Bing and H{\'e}lix-Nielsen, Claus and Hickey, Robert and Hinds, Bruce and Hirunpinyopas, Wisit and Horner, Andreas and Hou, Jun-Li and Hummer, Gerhard and Iamprasertkun, Pawin and Kazushi, Kinbara and Kumar, Manish and Legrand, Yves-Marie and Lokesh, Mahesh and Mi, Baoxia and Mitra, Sushanta and Murail, Samuel and Noy, Aleksandr and Nunes, Suzana and Pohl, Peter and Song, Qilei and Song, Woochul and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish} } @inbook {2018|2082, title = {Biomimetic water channels: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {205-229}, issn = {1364-5498}, doi = {10.1039/c8fd90020e}, author = {Marc Baaden and Barboiu, Mihail and Bill, Roslyn M and Chen, Chun-Long and Davis, Jeffery and Di Vincenzo, Maria and Freger, Viatcheslav and Fr{\"o}ba, Michael and Gale, Philip A and Gong, Bing and H{\'e}lix-Nielsen, Claus and Hickey, Robert and Hinds, Bruce and Hou, Jun-Li and Hummer, Gerhard and Kumar, Manish and Legrand, Yves-Marie and Lokesh, Mahesh and Mi, Baoxia and Murail, Samuel and Pohl, Peter and Sansom, Mark and Song, Qilei and Song, Woochul and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish and V{\"o}gele, Martin} } @article {2018|2112, title = {Breaking down cellulose fibrils with a mid-infrared laser}, journal = {Cellulose}, volume = {25}, year = {2018}, pages = {5553{\textendash}5568}, author = {Domin, Dominik and Man, Viet Hoang and Van-Oanh, Nguyen-Thi and Wang, Junmei and Kawasaki, Takayasu and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2018|2046, title = {Controlling Redox Enzyme Orientation at Planar Electrodes}, journal = {Catalysts}, volume = {8}, year = {2018}, abstract = {

Redox enzymes, which catalyze reactions involving electron transfers in living organisms, are very promising components of biotechnological devices, and can be envisioned for sensing applications as well as for energy conversion. In this context, one of the most significant challenges is to achieve efficient direct electron transfer by tunneling between enzymes and conductive surfaces. Based on various examples of bioelectrochemical studies described in the recent literature, this review discusses the issue of enzyme immobilization at planar electrode interfaces. The fundamental importance of controlling enzyme orientation, how to obtain such orientation, and how it can be verified experimentally or by modeling are the three main directions explored. Since redox enzymes are sizable proteins with anisotropic properties, achieving their functional immobilization requires a specific and controlled orientation on the electrode surface. All the factors influenced by this orientation are described, ranging from electronic conductivity to efficiency of substrate supply. The specificities of the enzymatic molecule, surface properties, and dipole moment, which in turn influence the orientation, are introduced. Various ways of ensuring functional immobilization through tuning of both the enzyme and the electrode surface are then described. Finally, the review deals with analytical techniques that have enabled characterization and quantification of successful achievement of the desired orientation. The rich contributions of electrochemistry, spectroscopy (especially infrared spectroscopy), modeling, and microscopy are featured, along with their limitations.

}, issn = {2073-4344}, doi = {10.3390/catal8050192}, url = {http://www.mdpi.com/2073-4344/8/5/192}, author = {Hitaishi, Vivek Pratap and Clement, Romain and Bourassin, Nicolas and Marc Baaden and de Poulpiquet, Anne and S Sacquin-Mora and Ciaccafava, Alexandre and Lojou, Elisabeth} } @article {2018|2093, title = {Dystrophin{\textquoteright}s central domain forms a complex filament that becomes disorganized by in-frame deletions.}, journal = {J Biol Chem}, volume = {293}, year = {2018}, month = {2018 05 04}, pages = {6637-6646}, abstract = {

Dystrophin, encoded by the gene, is critical for maintaining plasma membrane integrity during muscle contraction events. Mutations in the gene disrupting the reading frame prevent dystrophin production and result in severe Duchenne muscular dystrophy (DMD); in-frame internal deletions allow production of partly functional internally deleted dystrophin and result in less severe Becker muscular dystrophy (BMD). Many known BMD deletions occur in dystrophin\&$\#$39;s central domain, generally considered to be a monotonous rod-shaped domain based on the knowledge of spectrin family proteins. However, the effects caused by these deletions, ranging from asymptomatic to severe BMD, argue against the central domain serving only as a featureless scaffold. We undertook structural studies combining small-angle X-ray scattering and molecular modeling in an effort to uncover the structure of the central domain, as dystrophin has been refractory to characterization. We show that this domain appears to be a tortuous and complex filament that is profoundly disorganized by the most severe BMD deletion (loss of exons 45-47). Despite the preservation of large parts of the binding site for neuronal nitric oxide synthase (nNOS) in this deletion, computational approaches failed to recreate the association of dystrophin with nNOS. This observation is in agreement with a strong decrease of nNOS immunolocalization in muscle biopsies, a parameter related to the severity of BMD phenotypes. The structural description of the whole dystrophin central domain we present here is a first necessary step to improve the design of microdystrophin constructs toward the goal of a successful gene therapy for DMD.

}, keywords = {Binding Sites, Dystrophin, Exons, Gene Deletion, Humans, Molecular Docking Simulation, Muscular Dystrophy, Duchenne, Nitric Oxide Synthase Type I, Protein Domains, Reading Frames, Scattering, Small Angle, Solutions, X-Ray Diffraction}, issn = {1083-351X}, doi = {10.1074/jbc.M117.809798}, author = {Delalande, Olivier and Molza, Anne-Elisabeth and Dos Santos Morais, Raphael and Ch{\'e}ron, Ang{\'e}lique and Pollet, {\'E}meline and Raguenes-Nicol, C{\'e}line and Tascon, Christophe and Giudice, Emmanuel and Guilbaud, Marine and Nicolas, Aur{\'e}lie and Bondon, Arnaud and Leturcq, France and Nicolas F{\'e}rey and Marc Baaden and Perez, Javier and Roblin, Pierre and Pi{\'e}tri-Rouxel, France and Hubert, Jean-Fran{\c c}ois and Czjzek, Mirjam and Le Rumeur, Elisabeth} } @article {2018|2136, title = {Forcing the reversibility of a mechanochemical reaction}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {08}, pages = {3155}, abstract = {

Mechanical force modifies the free-energy surface of chemical reactions, often enabling thermodynamically unfavoured reaction pathways. Most of our molecular understanding of force-induced reactivity is restricted to the irreversible homolytic scission of covalent bonds and ring-opening in polymer mechanophores. Whether mechanical force can by-pass thermodynamically locked reactivity in heterolytic bimolecular reactions and how this impacts the reaction reversibility remains poorly understood. Using single-molecule force-clamp spectroscopy, here we show that mechanical force promotes the thermodynamically disfavored SN2 cleavage of an individual protein disulfide bond by poor nucleophilic organic thiols. Upon force removal, the transition from the resulting high-energy unstable mixed disulfide product back to the initial, low-energy disulfide bond reactant becomes suddenly spontaneous, rendering the reaction fully reversible. By rationally varying the nucleophilicity of a series of small thiols, we demonstrate how force-regulated chemical kinetics can be finely coupled with thermodynamics to predict and modulate the reversibility of bimolecular mechanochemical reactions.

}, doi = {10.1038/s41467-018-05115-6}, author = {Beedle, Amy E M and Mora, Marc and Davis, Colin T and Snijders, Ambrosius P and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @article {2018|2034, title = {Influence of electric field on the amyloid-β(29-42) peptides embedded in a membrane bilayer.}, journal = {J Chem Phys}, volume = {148}, year = {2018}, month = {2018 Jan 28}, pages = {045105}, abstract = {

Alzheimer\&$\#$39;s disease is linked to various types of aggregates of amyloid-β (Aβ) peptide and their interactions with protein receptors and neuronal cell membranes. Little is known on the impact of the electric field on membrane-embedded Aβ. Here we use atomistic molecular dynamics simulations to study the effects of a constant electric field on the conformations of Aβdimer inside a membrane, where the electric field has a strength of 20 mV/nm which exists across the membrane of a human neuron. Starting from α-helix peptides, the transmembrane electric field (TMEF) accelerates the conversion from the Gly-out substate to the Gly-side and Gly-in substates. Starting from β-sheet peptides, TMEF induces changes of the kink and tilt angles at Gly33 and Gly37. Overall, in the simulations totaling 10 μs, TMEF establishes new ground states for the dimer, similar to induced-fit in ligand binding. Our findings indicate that TMEF can stabilize rare conformations of amyloid peptides, and this could influence the cleavage of the amyloid precursor protein and the formation of β-sheet oligomers in membrane bilayers.

}, issn = {1089-7690}, doi = {10.1063/1.5018459}, author = {Lu, Yan and Shi, Xiao-Feng and Salsbury, Freddie R and Philippe Derreumaux} } @article {2018|2044, title = {Meet-U: Educating through research immersion}, journal = {PLOS Computational Biology}, volume = {14}, year = {2018}, month = {03}, pages = {1-10}, abstract = {

We present a new educational initiative called Meet-U that aims to train students for collaborative work in computational biology and to bridge the gap between education and research. Meet-U mimics the setup of collaborative research projects and takes advantage of the most popular tools for collaborative work and of cloud computing. Students are grouped in teams of 4\–5 people and have to realize a project from A to Z that answers a challenging question in biology. Meet-U promotes \"coopetition,\" as the students collaborate within and across the teams and are also in competition with each other to develop the best final product. Meet-U fosters interactions between different actors of education and research through the organization of a meeting day, open to everyone, where the students present their work to a jury of researchers and jury members give research seminars. This very unique combination of education and research is strongly motivating for the students and provides a formidable opportunity for a scientific community to unite and increase its visibility. We report on our experience with Meet-U in two French universities with master\’s students in bioinformatics and modeling, with protein\–protein docking as the subject of the course. Meet-U is easy to implement and can be straightforwardly transferred to other fields and/or universities. All the information and data are available at www.meet-u.org.

}, doi = {10.1371/journal.pcbi.1005992}, url = {https://doi.org/10.1371/journal.pcbi.1005992}, author = {Abdollahi, Nika and Albani, Alexandre and Anthony, Eric and Baud, Agnes and Cardon, M{\'e}lissa and Clerc, Robert and Czernecki, Dariusz and Conte, Romain and David, Laurent and Delaune, Agathe and Djerroud, Samia and Fourgoux, Pauline and Guiglielmoni, Nad{\`e}ge and Laurentie, Jeanne and Lehmann, Nathalie and Lochard, Camille and Montagne, R{\'e}mi and Myrodia, Vasiliki and Opuu, Vaitea and Parey, Elise and Polit, L{\'e}lia and Priv{\'e}, Sylvain and Quignot, Chlo{\'e} and Ruiz-Cuevas, Maria and Sissoko, Mariam and Sompairac, Nicolas and Vallerix, Audrey and Verrecchia, Violaine and Delarue, Marc and Gu{\'e}rois, Raphael and Ponty, Yann and S Sacquin-Mora and Carbone, Alessandra and Froidevaux, Christine and Le Crom, St{\'e}phane and Lespinet, Olivier and Weigt, Martin and Abboud, Samer and Bernardes, Juliana and Bouvier, Guillaume and Dequeker, Chlo{\'e} and Ferr{\'e}, Arnaud and Fuchs, Patrick and Lelandais, Ga{\"e}lle and Poulain, Pierre and Richard, Hugues and Schweke, Hugo and Laine, Elodie and Lopes, Anne} } @article {2018|2091, title = {MinOmics, an Integrative and Immersive Tool for Multi-Omics Analysis.}, journal = {J Integr Bioinform}, volume = {15}, year = {2018}, month = {2018 Jun 21}, abstract = {

Proteomic and transcriptomic technologies resulted in massive biological datasets, their interpretation requiring sophisticated computational strategies. Efficient and intuitive real-time analysis remains challenging. We use proteomic data on 1417 proteins of the green microalga Chlamydomonas reinhardtii to investigate physicochemical parameters governing selectivity of three cysteine-based redox post translational modifications (PTM): glutathionylation (SSG), nitrosylation (SNO) and disulphide bonds (SS) reduced by thioredoxins. We aim to understand underlying molecular mechanisms and structural determinants through integration of redox proteome data from gene- to structural level. Our interactive visual analytics approach on an 8.3 m2 display wall of 25 MPixel resolution features stereoscopic three dimensions (3D) representation performed by UnityMol WebGL. Virtual reality headsets complement the range of usage configurations for fully immersive tasks. Our experiments confirm that fast access to a rich cross-linked database is necessary for immersive analysis of structural data. We emphasize the possibility to display complex data structures and relationships in 3D, intrinsic to molecular structure visualization, but less common for omics-network analysis. Our setup is powered by MinOmics, an integrated analysis pipeline and visualization framework dedicated to multi-omics analysis. MinOmics integrates data from various sources into a materialized physical repository. We evaluate its performance, a design criterion for the framework.

}, keywords = {Algal Proteins, Chlamydomonas reinhardtii, Computer Graphics, Imaging, Three-Dimensional, Models, Structural, Oxidation-Reduction, Protein Conformation, Protein Interaction Maps, Protein Processing, Post-Translational, Proteome, Proteomics, Software, Virtual Reality}, issn = {1613-4516}, doi = {10.1515/jib-2018-0006}, author = {Maes, Alexandre and Martinez, Xavier and Druart, Karen and Laurent, Benoist and Gu{\'e}gan, Sean and Marchand, Christophe H and Lemaire, St{\'e}phane D and Marc Baaden} } @article {2018|2035, title = {Molecular Mechanism of Protein Unfolding under Shear: A Lattice Boltzmann Molecular Dynamics Study.}, journal = {J Phys Chem B}, volume = {122}, year = {2018}, month = {2018 Feb 08}, pages = {1573-1579}, abstract = {

Proteins are marginally stable soft-matter entities that can be disrupted using a variety of perturbative stresses, including thermal, chemical, or mechanical ones. Fluid under extreme flow conditions is a possible route to probe the weakness of biomolecules and collect information on the molecular cohesive interactions that secure their stability. Moreover, in many cases, physiological flow triggers the functional response of specialized proteins as occurring in blood coagulation or cell adhesion. We deploy the Lattice Boltzmann molecular dynamics technique based on the coarse-grained model for protein OPEP to study the mechanism of protein unfolding under Couette flow. Our simulations provide a clear view of how structural elements of the proteins are affected by shear, and for the simple study case, the β-hairpin, we exploited the analogy to pulling experiments to quantify the mechanical forces acting on the protein under shear.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b10796}, author = {Sterpone, Fabio and Philippe Derreumaux and Melchionna, Simone} } @article {2018|2111, title = {Molecular mechanism of the cell membrane pore formation induced by bubble stable cavitation}, journal = {The Journal of Physical Chemistry B}, volume = {123}, year = {2018}, pages = {71{\textendash}78}, author = {Man, Viet Hoang and Truong, Phan Minh and Li, Mai Suan and Wang, Junmei and Van-Oanh, Nguyen-Thi and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2018|2129, title = {Probing the quality control mechanism of the twin-arginine translocase with folding variants of a -designed heme protein.}, journal = {J Biol Chem}, volume = {293}, year = {2018}, month = {2018 05 04}, pages = {6672-6681}, abstract = {

Protein transport across the cytoplasmic membrane of bacterial cells is mediated by either the general secretion (Sec) system or the twin-arginine translocase (Tat). The Tat machinery exports folded and cofactor-containing proteins from the cytoplasm to the periplasm by using the transmembrane proton motive force as a source of energy. The Tat apparatus apparently senses the folded state of its protein substrates, a quality-control mechanism that prevents premature export of nascent unfolded or misfolded polypeptides, but its mechanistic basis has not yet been determined. Here, we investigated the innate ability of the model Tat system to recognize and translocate -designed protein substrates with experimentally determined differences in the extent of folding. Water-soluble, four-helix bundle maquette proteins were engineered to bind two, one, or no heme cofactors, resulting in a concomitant reduction in the extent of their folding, assessed with temperature-dependent CD spectroscopy and one-dimensional H NMR spectroscopy. Fusion of the archetypal N-terminal Tat signal peptide of the trimethylamine--oxide (TMAO) reductase (TorA) to the N terminus of the protein maquettes was sufficient for the Tat system to recognize them as substrates. The clear correlation between the level of Tat-dependent export and the degree of heme -induced folding of the maquette protein suggested that the membrane-bound Tat machinery can sense the extent of folding and conformational flexibility of its substrates. We propose that these artificial proteins are ideal substrates for future investigations of the Tat system\&$\#$39;s quality-control mechanism.

}, keywords = {Amino Acid Sequence, Bacterial Proteins, Circular Dichroism, Escherichia coli, Escherichia coli Proteins, Heme-Binding Proteins, Hemeproteins, Membrane Transport Proteins, Methylamines, Models, Molecular, Oxidoreductases, N-Demethylating, Periplasm, Protein Folding, Protein Sorting Signals, Protein Stability, Protein Transport, Proton Magnetic Resonance Spectroscopy, Substrate Specificity, Temperature}, issn = {1083-351X}, doi = {10.1074/jbc.RA117.000880}, author = {Sutherland, George A and Grayson, Katie J and Adams, Nathan B P and Mermans, Daphne M J and Jones, Alexander S and Robertson, Angus J and Auman, Dirk B and Brindley, Amanda A and Sterpone, Fabio and Tuffery, Pierre and Philippe Derreumaux and Dutton, P Leslie and Robinson, Colin and Hitchcock, Andrew and Hunter, C Neil} } @article {2018|2114, title = {Rayleigh-Plesset equation of the bubble stable cavitation in water: A nonequilibrium all-atom molecular dynamics simulation study}, journal = {The Journal of Chemical Physics}, volume = {148}, year = {2018}, pages = {094505}, author = {Man, Viet Hoang and Li, Mai Suan and Philippe Derreumaux and Phuong Hoang Nguyen} } @booklet {2018|2066, title = {Ten simple rules to create a serious game, illustrated with examples from structural biology}, year = {2018}, author = {Marc Baaden and Delalande, Olivier and Nicolas F{\'e}rey and Pasquali, Samuela and Waldisp{\"u}hl, J{\'e}r{\^o}me and Antoine Taly} } @article {2018|2138, title = {Three Weaknesses for Three Perturbations: Comparing Protein Unfolding Under Shear, Force, and Thermal Stresses}, journal = {J Phys Chem B}, volume = {122}, year = {2018}, month = {Dec}, pages = {11922-11930}, abstract = {

The perturbation of a protein conformation by a physiological fluid flow is crucial in various biological processes including blood clotting and bacterial adhesion to human tissues. Investigating such mechanisms by computer simulations is thus of great interest, but it requires development of ad hoc strategies to mimic the complex hydrodynamic interactions acting on the protein from the surrounding flow. In this study, we apply the Lattice Boltzmann Molecular Dynamics (LBMD) technique built on the implicit solvent coarse-grained model for protein Optimized Potential for Efficient peptide structure Prediction (OPEP) and a mesoscopic representation of the fluid solvent, to simulate the unfolding of a small globular cold-shock protein in shear flow and to compare it to the unfolding mechanisms caused either by mechanical or thermal perturbations. We show that each perturbation probes a specific weakness of the protein and causes the disruption of the native fold along different unfolding pathways. Notably, the shear flow and the thermal unfolding exhibit very similar pathways, while because of the directionality of the perturbation, the unfolding under force is quite different. For force and thermal disruption of the native state, the coarse-grained simulations are compared to all-atom simulations in explicit solvent, showing an excellent agreement in the explored unfolding mechanisms. These findings encourage the use of LBMD based on the OPEP model to investigate how a flow can affect the function of larger proteins, for example, in catch-bond systems.

}, doi = {10.1021/acs.jpcb.8b08711}, author = {Languin-Catto{\"e}n, Olivier and Melchionna, Simone and Philippe Derreumaux and Guillaume Stirnemann and Sterpone, Fabio} } @article {2017|2024, title = {Ab Initio Simulations of Water Dynamics in Aqueous TMAO Solutions: Temperature and Concentration Effects}, journal = {J Phys Chem B}, year = {2017}, month = {Dec}, abstract = {

We use ab initio molecular dynamics simulation to study the effect of hydrophobic groups on the dynamics of water molecules in aqueous solutions of trimethylamine N-oxide (TMAO). We show that hydrophobic groups induce a moderate (\<2-fold) slowdown of water reorientation and hydrogen-bond dynamics in dilute solutions, but that this slowdown rapidly increases with solute concentration. In addition, the slowdown factor is found to vary very little with temperature, thus suggesting an entropic origin. All of these results are in quantitative agreement with prior classical molecular dynamics simulations and with the previously suggested excluded-volume model. The hydrophilic TMAO headgroup is found to affect water dynamics more strongly than the hydrophobic moiety, and the magnitude of this slowdown is very sensitive to the strength of the water-solute hydrogen-bond.

}, doi = {10.1021/acs.jpcb.7b09989}, author = {Guillaume Stirnemann and Elise Dubou{\'e}-Dijon and Laage, Damien} } @article {2017|2022, title = {ATP hydrolysis provides functions that promote rejection of pairings between different copies of long repeated sequences}, journal = {Nucleic Acids Res}, volume = {45}, year = {2017}, pages = {8448-8462}, abstract = {

During DNA recombination and repair, RecA family proteins must promote rapid joining of homologous DNA. Repeated sequences with \>100 base pair lengths occupy more than 1\% of bacterial genomes; however, commitment to strand exchange was believed to occur after testing ~20-30 bp. If that were true, pairings between different copies of long repeated sequences would usually become irreversible. Our experiments reveal that in the presence of ATP hydrolysis even 75 bp sequence-matched strand exchange products remain quite reversible. Experiments also indicate that when ATP hydrolysis is present, flanking heterologous dsDNA regions increase the reversibility of sequence matched strand exchange products with lengths up to ~75 bp. Results of molecular dynamics simulations provide insight into how ATP hydrolysis destabilizes strand exchange products. These results inspired a model that shows how pairings between long repeated sequences could be efficiently rejected even though most homologous pairings form irreversible products.

}, doi = {10.1093/nar/gkx582}, author = {Danilowicz, Claudia and Hermans, Laura and Coljee, Vincent and Chantal Pr{\'e}vost and Prentiss, Mara} } @article {2017|2039, title = {A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against.}, journal = {Bioinform Biol Insights}, volume = {11}, year = {2017}, month = {2017}, pages = {1177932217712471}, abstract = {

We present an approach for detecting enzymes that are specific ofcompared withand provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific forcompared with, only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific ofand 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with. Among the 40 strictly specific enzymes, we identified sterol 24-C-methyltransferase, pyruvate phosphate dikinase, trypanothione synthetase, and RNA-editing ligase as 4 essential enzymes forthat may serve as targets for drug development.

}, issn = {1177-9322}, doi = {10.1177/1177932217712471}, author = {Catharina, Larissa and Lima, Carlyle Ribeiro and Franca, Alexander and Guimar{\~a}es, Ana Carolina Ramos and Alves-Ferreira, Marcelo and Tuffery, Pierre and Philippe Derreumaux and Carels, Nicolas} } @article {2017|2032, title = {Conformational Ensembles of the Wild-Type and S8C Aβ1-42 Dimers.}, journal = {J Phys Chem B}, volume = {121}, year = {2017}, month = {2017 Mar 23}, pages = {2434-2442}, abstract = {

We characterized the dimer of the amyloid-β wild-type (WT) peptide, Aβ, of 42 residues and its disulfide-bond-locked double mutant (S8C) by replica exchange molecular dynamics simulations. Aβ dimers are known to be the smallest toxic species in Alzheimer\&$\#$39;s disease, and the S8C mutant has been shown experimentally to form an exclusive homogeneous and neurotoxic dimer. Our 50 μs all-atom simulations reveal similar secondary structures and collision cross-sections but very different intramolecular and intermolecular conformations upon double S8C mutation. Both dimers are very dynamic with hundreds of free-energy minima that differ from the U-shape and S-shape conformations of the peptides in the fibrils. The only common structural feature, shared by both species with a probability of 4\% in WT and 12\% in S8C-S8C, is a three-stranded β-sheet spanning the 17-23, 29-36, and 39-41 residues, which does not exist in the Aβ40 WT dimers.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b00267}, author = {Man, Viet Hoang and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2017|2020, title = {Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {May}, pages = {1858}, author = {Colloc{\textquoteright}h, N. and S Sacquin-Mora and Avella, G. and Dhaussy, A. C. and Prange, T. and Vallone, B. and Girard, E.} } @article {2017|2041, title = {Fast coarse-grained model for RNA titration.}, journal = {J Chem Phys}, volume = {146}, year = {2017}, month = {2017 Jan 21}, pages = {035101}, abstract = {

A new numerical scheme for RNA (ribonucleic acid) titration based on the Debye-H{\"u}ckel framework for the salt description is proposed in an effort to reduce the computational costs for further applications to study protein-RNA systems. By means of different sets of Monte Carlo simulations, we demonstrated that this new scheme is able to correctly reproduce the experimental titration behavior and salt pKshifts. In comparison with other theoretical approaches, similar or even better outcomes are achieved at much lower computational costs. The model was tested on the lead-dependent ribozyme, the branch-point helix, and the domain 5 from Azotobacter vinelandii Intron 5.

}, keywords = {Azotobacter vinelandii, Introns, Models, Chemical, Molecular Dynamics Simulation, Monte Carlo Method, Protein Structure, Secondary, Protons, RNA, RNA, Catalytic, Titrimetry}, issn = {1089-7690}, doi = {10.1063/1.4972986}, author = {Barroso da Silva, Fernando Luis and Philippe Derreumaux and Pasquali, Samuela} } @article {2017|2031, title = {High-Resolution Structures of the Amyloid-β 1-42 Dimers from the Comparison of Four Atomistic Force Fields.}, journal = {J Phys Chem B}, volume = {121}, year = {2017}, month = {2017 Jun 22}, pages = {5977-5987}, abstract = {

The dimer of the amyloid-β peptide Aβ of 42 residues is the smallest toxic species in Alzheimer\&$\#$39;s disease, but its equilibrium structures are unknown. Here we determined the equilibrium ensembles generated by the four atomistic OPLS-AA, CHARMM22*, AMBER99sb-ildn, and AMBERsb14 force fields with the TIP3P water model. On the basis of 144 μs replica exchange molecular dynamics simulations (with 750 ns per replica), we find that the four force fields lead to random coil ensembles with calculated cross-collision sections, hydrodynamics properties, and small-angle X-ray scattering profiles independent of the force field. There are, however, marked differences in secondary structure, with the AMBERsb14 and CHARMM22* ensembles overestimating the CD-derived helix content, and the OPLS-AA and AMBER99sb-ildn secondary structure contents in agreement with CD data. Also the intramolecular beta-hairpin content spanning residues 17-21 and 30-36 varies between 1.5\% and 13\%. Overall, there are significant differences in tertiary and quaternary conformations among all force fields, and the key finding, irrespective of the force field, is that the dimer is stabilized by nonspecific interactions, explaining therefore its possible transient binding to multiple cellular partners and, in part, its toxicity.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b04689}, author = {Man, Viet Hoang and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2017|2021, title = {A membrane-inserted structural model of the yeast mitofusin Fzo1}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Aug 31}, pages = {10217}, type = {Research Article}, abstract = {

Mitofusins are large transmembrane GTPases of the dynamin-related protein family, and are required for the tethering and fusion of mitochondrial outer membranes. Their full-length structures remain unknown, which is a limiting factor in the study of outer membrane fusion. We investigated the structure and dynamics of the yeast mitofusin Fzo1 through a hybrid computational and experimental approach, combining molecular modelling and all-atom molecular dynamics simulations in a lipid bilayer with site-directed mutagenesis and in vivo functional assays. The predicted architecture of Fzo1 improves upon the current domain annotation, with a precise description of the helical spans linked by flexible hinges, which are likely of functional significance. In vivo site-directed mutagenesis validates salient aspects of this model, notably, the long-distance contacts and residues participating in hinges. GDP is predicted to interact with Fzo1 through the G1 and G4 motifs of the GTPase domain. The model reveals structural determinants critical for protein function, including regions that may be involved in GTPase domain-dependent rearrangements.

}, issn = {2045-2322}, doi = {10.1038/s41598-017-10687-2}, author = {De Vecchis, Dario and Cavellini, Laetitia and Marc Baaden and J{\'e}r{\^o}me H{\'e}nin and Cohen, Micka{\"e}l M and Antoine Taly} } @article {2017|2037, title = {Multifunctional energy landscape for a DNA G-quadruplex: An evolved molecular switch.}, journal = {J Chem Phys}, volume = {147}, year = {2017}, month = {2017 Oct 21}, pages = {152715}, abstract = {

We explore the energy landscape for a four-fold telomere repeat, obtaining interconversion pathways between six experimentally characterised G-quadruplex topologies. The results reveal a multi-funnel system, with a variety of intermediate configurations and misfolded states. This organisation is identified with the intrinsically multi-functional nature of the system, suggesting a new paradigm for the classification of such biomolecules and clarifying issues regarding apparently conflicting experimental results.

}, issn = {1089-7690}, doi = {10.1063/1.4997377}, author = {Cragnolini, Tristan and Chakraborty, Debayan and Sponer, Jiri and Philippe Derreumaux and Pasquali, Samuela and Wales, David J} } @article {2017|2029, title = {Multi-scale simulations of biological systems using the OPEP coarse-grained model.}, journal = {Biochem Biophys Res Commun}, year = {2017}, month = {2017 Sep 14}, abstract = {

Biomolecules are complex machines that are optimized by evolution to properly fulfill or contribute to a variety of biochemical tasks in the cellular environment. Computer simulations based on quantum mechanics and atomistic force fields have been proven to be a powerful microscope for obtaining valuable insights into many biological, physical, and chemical processes. Many interesting phenomena involve, however, a time scale and a number of degrees of freedom, notably if crowding is considered, that cannot be explored at an atomistic resolution. To bridge the gap between reality and simulation, many different advanced computational techniques and coarse-grained (CG) models have been developed. Here, we report some applications of the CG OPEP protein model to amyloid fibril formation, the response of catch-bond proteins to two types of fluid flow, and interactive simulations to fold peptides with well-defined 3D structures or with intrinsic disorder.

}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2017.08.165}, author = {Sterpone, Fabio and Doutreligne, S{\'e}bastien and Tran, Thanh Thuy and Melchionna, Simone and Marc Baaden and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2017|2038, title = {Protein-RNA complexation driven by the charge regulation mechanism.}, journal = {Biochem Biophys Res Commun}, year = {2017}, month = {2017 Jul 12}, abstract = {

Electrostatic interactions play a pivotal role in many (bio)molecular association processes. The molecular organization and function in biological systems are largely determined by these interactions from pure Coulombic contributions to more peculiar mesoscopic forces due to ion-ion correlation and proton fluctuations. The latter is a general electrostatic mechanism that gives attraction particularly at low electrolyte concentrations. This charge regulation mechanism due to titrating amino acid and nucleotides residues is discussed here in a purely electrostatic framework. By means of constant-pH Monte Carlo simulations based on a fast coarse-grained titration proton scheme, a new computer molecular model was devised to study protein-RNA interactions. The complexation between the RNA silencing suppressor p19 viral protein and the 19-bp small interfering RNA was investigated at different solution pH and salt conditions. The outcomes illustrate the importance of the charge regulation mechanism that enhances the association between these macromolecules in a similar way as observed for other protein-polyelectrolyte systems typically found in colloidal science. Due to the highly negative charge of RNA, the effect is more pronounced in this system as predicted by the Kirkwood-Shumaker theory. Our results contribute to the general physico-chemical understanding of macromolecular complexation and shed light on the extensive role of RNA in the cell\&$\#$39;s life.

}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2017.07.027}, author = {Barroso da Silva, Fernando Luis and Philippe Derreumaux and Pasquali, Samuela} } @article {2017|2095, title = {Residues of Alpha Helix H3 Determine Distinctive Features of Transforming Growth Factor β3.}, journal = {J Phys Chem B}, volume = {121}, year = {2017}, month = {2017 06 08}, pages = {5483-5498}, abstract = {

Transforming growth factors (TGF-βs) are proteins that regulate cell growth by binding to their receptors. In contrast to transforming growth factor (TGF) β1, TGF-β3 homodimer is believed to exist also in an open conformation, in which both of its monomers are loosely packed against each other. At the origin of this difference is the H3-helix. Its sequence and degree of structuration seem to govern the outcome of TGF dimerization. We docked two monomers of TGF-β3 with intact and altered H3 α-helix against each other using HADDOCK. TGF-β3 monomer with an intact H3-helix exclusively forms closed conformations of homodimer, whereas the open conformation may coexist with the closed one when a part of the H3 α-helix is destabilized. We quantify the difference in its conformational preference for the open versus the closed structure by calculating the binding energy between monomers using the MMPBSA approach. We compare the wild type (wt) TGFβ3/TGFβ1 homodimers in the Protein Data Bank to a swapped mutant where all residues of the H3-helix were mutated to the respective TGFβ1/TGFβ3 sequence. Swapping stabilizes the closed conformation and destabilizes the open conformation of TGFβ3. Further detailed insight is derived from molecular dynamics simulation studies suggesting that Val 61 of the H3-helix may act as an anchor residue for the closed conformation of TGFβ3. Computational alanine scanning mutagenesis confirms that several residues of the H3-helix are the hot residues for the closed conformation of TGFβ3. These observations may bear relevance to general conformational transitions in proteins and specifically in the TGFβ superfamily.

}, keywords = {Molecular Dynamics Simulation, Protein Conformation, alpha-Helical, Transforming Growth Factor beta3}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b01867}, author = {Nayeem, Shahid M and Oteri, Francesco and Marc Baaden and Deep, Shashank} } @article {2017|2040, title = {Small static electric field strength promotes aggregation-prone structures in amyloid-β(29-42).}, journal = {J Chem Phys}, volume = {146}, year = {2017}, month = {2017 Apr 14}, pages = {145101}, abstract = {

The formation of senile plaques in central neural system resulting from the aggregation of the amyloid β (Aβ) of 40 and 42 residues is one of the two hallmarks of Alzheimer\&$\#$39;s disease. Numerous experiments and computational studies have shown that the aggregation of Aβ peptides in vitro is very complex and depends on many factors such as pH, agitation, temperature, and peptide concentration. The impact of a static electric field (EF) on amyloid peptide aggregation has been much less studied, although EFs may have some applications to treat Parkinson\&$\#$39;s disease symptoms. Here, we study the influence of an EF strength of 20 mV/nm, present in the human brains, on the conformation of the Aβdimer. Our 7 μs non-equilibrium atomistic simulations in aqueous solution show that this field-strength promotes substantially the formation of β-hairpins, believed to be a very important intermediate state during aggregation. This work also suggests that structural biology experiments conducted under appropriate EF strengths may help reduce the conformational heterogeneity of Aβ/Aβdimers and provide significant insights into their structures that may be disease-causing.

}, issn = {1089-7690}, doi = {10.1063/1.4979866}, author = {Lu, Yan and Shi, Xiao-Feng and Salsbury, Freddie R and Philippe Derreumaux} } @article {2017|2096, title = {String method solution of the gating pathways for a pentameric ligand-gated ion channel.}, journal = {Proc Natl Acad Sci U S A}, volume = {114}, year = {2017}, month = {2017 05 23}, pages = {E4158-E4167}, abstract = {

Pentameric ligand-gated ion channels control synaptic neurotransmission by converting chemical signals into electrical signals. Agonist binding leads to rapid signal transduction via an allosteric mechanism, where global protein conformational changes open a pore across the nerve cell membrane. We use all-atom molecular dynamics with a swarm-based string method to solve for the minimum free-energy gating pathways of the proton-activated bacterial GLIC channel. We describe stable wetted/open and dewetted/closed states, and uncover conformational changes in the agonist-binding extracellular domain, ion-conducting transmembrane domain, and gating interface that control communication between these domains. Transition analysis is used to compute free-energy surfaces that suggest allosteric pathways; stabilization with pH; and intermediates, including states that facilitate channel closing in the presence of an agonist. We describe a switching mechanism that senses proton binding by marked reorganization of subunit interface, altering the packing of β-sheets to induce changes that lead to asynchronous pore-lining M2 helix movements. These results provide molecular details of GLIC gating and insight into the allosteric mechanisms for the superfamily of pentameric ligand-gated channels.

}, keywords = {Computer Simulation, Ligand-Gated Ion Channels, Models, Biological, Models, Chemical}, issn = {1091-6490}, doi = {10.1073/pnas.1617567114}, author = {Lev, Bogdan and Murail, Samuel and Poitevin, Fr{\'e}d{\'e}ric and Cromer, Brett A and Marc Baaden and Delarue, Marc and Allen, Toby W} } @article {2017|2036, title = {VLITL is a major cross-β-sheet signal for fibrinogen Aα-chain frameshift variants.}, journal = {Blood}, volume = {130}, year = {2017}, month = {2017 12 21}, pages = {2799-2807}, abstract = {

The first case of hereditary fibrinogen Aα-chain amyloidosis was recognized \>20 years ago, but disease mechanisms still remain unknown. Here we report detailed clinical and proteomics studies of a French kindred with a novel amyloidogenic fibrinogen Aα-chain frameshift variant, Phe521Leufs, causing a severe familial form of renal amyloidosis. Next, we focused our investigations to elucidate the molecular basis that render this Aα-chain variant amyloidogenic. We show that a 49-mer peptide derived from the C-terminal part of the Phe521Leufs chain is deposited as fibrils in the patient\&$\#$39;s kidneys, establishing that only a small portion of Phe521Leufs directly contributes to amyloid formation in vivo. In silico analysis indicated that this 49-mer Aα-chain peptide contained a motif (VLITL), with a high intrinsic propensity for β-aggregation at residues 44 to 48 of human renal fibrils. To experimentally verify the amyloid propensity of VLITL, we generated synthetic Phe521Leufs-derived peptides and compared their capacity for fibril formation in vitro with that of their VLITL-deleted counterparts. We show that VLITL forms typical amyloid fibrils in vitro and is a major signal for cross-β-sheet self-association of the 49-mer Phe521Leufs peptide identified in vivo, whereas its absence abrogates fibril formation. This study provides compelling evidence that VLITL confers amyloidogenic properties to Aα-chain frameshift variants, yielding a previously unknown molecular basis for the pathogenesis of Aα-chain amyloidosis.

}, keywords = {Amino Acid Motifs, Amino Acid Sequence, Amyloid, Amyloidosis, Familial, Fibrinogen, Frameshift Mutation, Humans, Kidney, Protein Conformation, beta-Strand}, issn = {1528-0020}, doi = {10.1182/blood-2017-07-796185}, author = {Garnier, Cyrille and Briki, Fatma and Nedelec, Brigitte and Le Pogamp, Patrick and Dogan, Ahmet and Rioux-Leclercq, Nathalie and Goude, Renan and Beugnet, Caroline and Martin, Laurent and Delpech, Marc and Bridoux, Frank and Grateau, Gilles and Doucet, Jean and Philippe Derreumaux and Valleix, Sophie} } @article {2017|2042, title = {What Can Human-Guided Simulations Bring to RNA Folding?}, journal = {Biophys J}, volume = {113}, year = {2017}, month = {2017 Jul 25}, pages = {302-312}, abstract = {

Inspired by the recent success of scientific-discovery games for predicting protein tertiary and RNA secondary structures, we have developed an open software for coarse-grained RNA folding simulations, guided by human intuition. To determine the extent to which interactive simulations can accurately predict 3D RNA structures of increasing complexity and lengths (four RNAs with 22-47 nucleotides), an interactive experiment was conducted with 141 participants who had very little knowledge of nucleic acids systems and computer simulations, and had received only a brief description of the important forces stabilizing RNA structures. Their structures and full trajectories have been analyzed statistically and compared to standard replica exchange molecular dynamics simulations. Our analyses show that participants gain easily chemical intelligence to fold simple and nontrivial topologies, with little computer time, and this result opens the door for the use of human-guided simulations to RNA folding. Our experiment shows that interactive simulations have better chances of success when the user widely explores the conformational space. Interestingly, providing on-the-fly feedback of the root mean square deviation with respect to the experimental structure did not improve the quality of the proposed models.

}, keywords = {Access to Information, Computer Simulation, Feedback, Psychological, Humans, Internet, Models, Genetic, Models, Molecular, RNA, RNA Folding, Software, Solvents}, issn = {1542-0086}, doi = {10.1016/j.bpj.2017.05.047}, author = {Mazzanti, Liuba and Doutreligne, S{\'e}bastien and Gageat, Cedric and Philippe Derreumaux and Antoine Taly and Marc Baaden and Pasquali, Samuela} } @article {2017|2030, title = {Why Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer{\textquoteright}s Disease?}, journal = {ACS Chem Neurosci}, volume = {8}, year = {2017}, month = {2017 Jul 19}, pages = {1435-1437}, abstract = {

The two hallmarks of Alzheimer\&$\#$39;s disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.

}, keywords = {Alzheimer Disease, Amyloid beta-Peptides, Animals, Drug Discovery, Humans, Neuroprotective Agents}, issn = {1948-7193}, doi = {10.1021/acschemneuro.7b00188}, author = {Doig, Andrew J and Del Castillo-Frias, Maria P and Berthoumieu, Olivia and Tarus, Bogdan and Nasica-Labouze, Jessica and Sterpone, Fabio and Phuong Hoang Nguyen and Hooper, Nigel M and Faller, Peter and Philippe Derreumaux} } @conference {2016|1606, title = {Alzheimer{\textquoteright}s Disease: Insights into Amyloid Fibril Formation from Lattice Monte Carlo Simulations}, booktitle = {Biophys. J.}, volume = {110}, number = {3, 1}, year = {2016}, note = {60th Annual Meeting of the Biophysical-Society, Los Angeles, CA, FEB 27-MAR 02, 2016}, month = {feb}, pages = {219A}, publisher = {Biophys Soc}, organization = {Biophys Soc}, issn = {0006-3495}, author = {Thanh-Thuy Tran and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2016|1656, title = {Coarse-grained and All-atom Simulations towards the Early and Late Steps of Amyloid Fibril Formation}, journal = {Isr. J. Chem.}, volume = {DOI: 10.1002/ijch.201600048.}, year = {2016}, author = {M. Chiricotto and Thanh-Thuy Tran and Phuong Hoang Nguyen and S. Melchionna and Fabio Sterpone and Philippe Derreumaux} } @article {2016|1707, title = {Coarse-Grained Simulations Complemented by Atomistic Molecular Dynamics Provide New Insights into Folding and Unfolding of Human Telomeric G-Quadruplexes}, journal = {J. Chem. Theory Comput.}, volume = {12}, number = {12}, year = {2016}, month = {dec}, pages = {6077{\textendash}6097}, abstract = {G-quadruplexes are the most important non canonical DNA architectures. Many quadruplex-forming sequences, including the human telomeric sequence d(GGGTTA)(n), have been investigated due to their implications in cancer and other diseases, and because of their potential in DNA-based nanotechnology. Despite the availability of atomistic structural studies of folded G-quadruplexes, their folding pathways remain mysterious, and mutually contradictory models of folding coexist in the literature. Recent experiments convincingly demonstrated that G-quadruplex folding often takes days to reach thermodynamic equilibrium. Based on atomistic simulations of diverse classes of intermediates in G-quadruplex folding, we have suggested that the folding is an extremely multipathway process combining a kinetic partitioning mechanism with conformational diffusion. However, complete G-quadruplex folding is far beyond the time scale of atomistic simulations. Here we use high-resolution coarse-grained simulations to investigate potential unfolding intermediates, whose structural dynamics are then further explored with all-atom simulations. This multiscale approach indicates how various pathways are interconnected in a complex network. Spontaneous conversions between different folds are observed. We demonstrate the inability of simple order parameters, such as radius of gyration or the number of native H-bonds, to describe the folding landscape of the G-quadruplexes. Our study also provides information relevant to further development of the coarse grained force field.}, issn = {1549-9618}, doi = {10.1021/acs.jctc.6b00667}, author = {Stadlbauer, Petr and Mazzanti, Liuba and Cragnolini, Tristan and Wales, David J. and Philippe Derreumaux and Pasquali, Samuela and Sponer, Jiri} } @article {2016|1712, title = {Dimerization Mechanism of Alzheimer A beta(40) Peptides: The High Content of Intrapeptide-Stabilized Conformations in A2V and A2T Heterozygous Dimers Retards Amyloid Fibril Formation}, journal = {J. Phys. Chem. B}, volume = {120}, number = {47}, year = {2016}, pages = {12111{\textendash}12126}, abstract = {Amyloid beta (A beta) oligomerization is associated with the origin and progression of Alzheimer{\textquoteright}s disease (AD). While the A2V mutation enhances aggregation kinetics and toxicity, mixtures of wild-type (WT) and A2V, and also WT and A2T, peptides retard fibril formation and protect against AD. In this study, we simulate the equilibrium ensemble of WT:A2T A beta(40) dimer by means of extensive atomistic replica exchange molecular dynamics and compare our results with previous equivalent simulations of A2V:A2V, WT:WT, and WT:A2V A beta(40) dimers for a total time scale of nearly 0.1 ms. Qualitative comparison of the resulting thermodynamic properties, such as the relative binding free energies, with the reported experimental kinetic and thermodynamic data affords us important insight into the conversion from slow-pathway to fast-pathway dimer conformations. The crucial reaction coordinate or driving force of such transformation turns out to be related to hydrophobic interpeptide interactions. Analysis of the equilibrium ensembles shows that the fast-pathway conformations contain interpeptide out-of-register antiparallel beta-sheet structures at short interpeptide distances. In contrast, the slow-pathway conformations are formed by the association of peptides at large interpeptide distances and high intrapeptide compactness, such as conformations containing intramolecular three-stranded beta-sheets which sharply distinguish fast (A2V:A2V and WT:WT) and slow (WT:A2T and WT:A2V) amyloid-forming sequences. Also, this analysis leads us to predict that a molecule stabilizing the intramolecular three-stranded beta-sheet or inhibiting the formation of an interpeptide beta-sheet spanning residues 17-20 and 31-37 would further reduce fibril formation and probably the cytotoxicity of A beta species.}, issn = {1520-6106}, doi = {10.1021/acs.jpcp.6b10722}, author = {Phuong Hoang Nguyen and Fabio Sterpone and Pouplana, Ramon and Philippe Derreumaux and Campanera, Josep M.} } @article {2016|1765, title = {Electrostatics analysis of the mutational and pH effects of the N-terminal domain self-association of the major ampullate spidroin}, journal = {Soft Matter}, volume = {12}, number = {25}, year = {2016}, pages = {5600{\textendash}5612}, abstract = {Spider silk is a fascinating material combining mechanical properties such as maximum strength and high toughness comparable or better than man-made materials, with biocompatible degradability characteristics. Experimental measurements have shown that pH triggers the dimer formation of the N-terminal domain (NTD) of the major ampullate spidroin 1 (MaSp 1). A coarse-grained model accounting for electrostatics, van der Waals and pH-dependent charge-fluctuation interactions, by means of Monte Carlo simulations, gave us a more comprehensive view of the NTD dimerization process. A detailed analysis of the electrostatic properties and free energy derivatives for the NTD homoassociation was carried out at different pH values and salt concentrations for the protein wild type and for several mutants. We observed an enhancement of dipole-dipole interactions at pH 6 due to the ionization of key amino acids, a process identified as the main driving force for dimerization. Analytical estimates based on the DVLO theory framework corroborate our findings. Molecular dynamics simulations using the OPEP coarse-grained force field for proteins show that the mutant E17Q is subject to larger structural fluctuations when compared to the wild type. Estimates of the association rate constants for this mutant were evaluated by the Debye-Smoluchowski theory and are in agreement with the experimental data when thermally relaxed structures are used instead of the crystallographic data. Our results can contribute to the design of new mutants with specific association properties.}, issn = {1744-683X}, doi = {10.1039/c6sm00860g}, author = {Barroso da Silva, Fernando Luis and Pasquali, Samuela and Philippe Derreumaux and Dias, Luis Gustavo} } @article {2016|1630, title = {Evaluation of the coarse-grained OPEP force field for protein-protein docking}, journal = {Bmc Biophysics}, volume = {9}, year = {2016}, month = {apr}, abstract = {Background: Knowing the binding site of protein-protein complexes helps understand their function and shows possible regulation sites. The ultimate goal of protein-protein docking is the prediction of the three-dimensional structure of a protein-protein complex. Docking itself only produces plausible candidate structures, which must be ranked using scoring functions to identify the structures that are most likely to occur in nature. Methods: In this work, we rescore rigid body protein-protein predictions using the optimized potential for efficient structure prediction (OPEP), which is a coarse-grained force field. Using a force field based on continuous functions rather than a grid-based scoring function allows the introduction of protein flexibility during the docking procedure. First, we produce protein-protein predictions using ZDOCK, and after energy minimization via OPEP we rank them using an OPEP-based soft rescoring function. We also train the rescoring function for different complex classes and demonstrate its improved performance for an independent dataset. Results: The trained rescoring function produces a better ranking than ZDOCK for more than 50 \% of targets, rising to over 70 \% when considering only enzyme/inhibitor complexes. Conclusions: This study demonstrates for the first time that energy functions derived from the coarse-grained OPEP force field can be employed to rescore predictions for protein-protein complexes.}, issn = {2046-1682}, doi = {10.1186/s13628-016-0029-y}, author = {Kynast, Philipp and Philippe Derreumaux and Strodel, Birgit} } @article {2016|1661, title = {Hybridizing Rapidly Exploring Random Trees and Basin Hopping Yields an Improved Exploration of Energy Landscapes}, journal = {J. Comput. Chem.}, volume = {37}, year = {2016}, month = {mar}, pages = {752}, chapter = {739}, abstract = {

The number of local minima of the potential energy landscape (PEL) of molecular systems generally grows exponentially with the number of degrees of freedom, so that a crucial property of PEL exploration algorithms is their ability to identify local minima, which are low lying and diverse. In this work, we pres- ent a new exploration algorithm, retaining the ability of basin hopping (BH) to identify local minima, and that of transition based rapidly exploring random trees (T-RRT) to foster the exploration of yet unexplored regions. This ability is obtained by interleaving calls to the extension procedures of BH and T- RRT, and we show tuning the balance between these two types of calls allows the algorithm to focus on low lying regions. Computational efficiency is obtained using state-of- the art data structures, in particular for searching approximate nearest neighbors in metric spaces. We present results for the BLN69, a protein model whose conformational space has dimension 207 and whose PEL has been studied exhaustively. On this system, we show that the propensity of our algorithm to explore low lying regions of the landscape significantly out- performs those of BH and T-RRT.

}, doi = {10.1002/jcc.24256}, author = {Christine A. Roth and Tom Dreyfus and Charles H. Robert and Fr{\'e}d{\'e}ric Cazals} } @conference {2016|1607, title = {Hydrodynamic Effects on Amyloid-beta Aggregation}, booktitle = {Biophys. J.}, volume = {110}, number = {3, 1}, year = {2016}, note = {60th Annual Meeting of the Biophysical-Society, Los Angeles, CA, FEB 27-MAR 02, 2016}, month = {feb}, pages = {219A}, publisher = {Biophys Soc}, organization = {Biophys Soc}, issn = {0006-3495}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Fabio Sterpone} } @article {2016|1702, title = {Hydrodynamic effects on beta-amyloid (16-22) peptide aggregation}, journal = {J. Chem. Phys.}, volume = {145}, number = {3}, year = {2016}, month = {jul}, abstract = {Computer simulations based on simplified representations are routinely used to explore the early steps of amyloid aggregation. However, when protein models with implicit solvent are employed, these simulations miss the effect of solvent induced correlations on the aggregation kinetics and lifetimes of metastable states. In this work, we apply the multi-scale Lattice Boltzmann Molecular Dynamics technique (LBMD) to investigate the initial aggregation phases of the amyloid A beta(16-22) peptide. LBMD includes naturally hydrodynamic interactions (HIs) via a kinetic on-lattice representation of the fluid kinetics. The peptides are represented by the flexible OPEP coarse-grained force field. First, we have tuned the essential parameters that control the coupling between the molecular and fluid evolutions in order to reproduce the experimental diffusivity of elementary species. The method is then deployed to investigate the effect of HIs on the aggregation of 100 and 1000 A beta(16-22) peptides. We show that HIs clearly impact the aggregation process and the fluctuations of the oligomer sizes by favouring the fusion and exchange dynamics of oligomers between aggregates. HIs also guide the growth of the leading largest cluster. For the 100 A beta(16-22) peptide system, the simulation of similar to 300 ns allowed us to observe the transition from ellipsoidal assemblies to an elongated and slightly twisted aggregate involving almost the totality of the peptides. For the 1000 A beta(16-22) peptides, a system of unprecedented size at quasi-atomistic resolution, we were able to explore a branched disordered fibril-like structure that has never been described by other computer simulations, but has been observed experimentally. Published by AIP Publishing.}, issn = {0021-9606}, doi = {10.1063/1.4958323}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Fabio Sterpone} } @article {2016|1578, title = {Impact of the A2V Mutation on the Heterozygous and Homozygous A beta 1-40 Dimer Structures from Atomistic Simulations}, journal = {Acs Chem. Neurosci.}, volume = {7}, number = {6}, year = {2016}, month = {jun}, pages = {823{\textendash}832}, abstract = {The A2V mutation was reported to protect from Alzheimer{\textquoteright}s disease in its heterozygous form and cause an early Alzheimer{\textquoteright}s disease type dementia in its homozygous form. Experiments showed that the aggregation rate follows the order A2V > WT (wild-type) > A2V-WT. To understand the impact of this mutation, we carried out replica exchange molecular dynamics simulations of A beta 1-40 WT-A2V and A2V-A2V dimers and compared to the WT dimer. Our atomistic simulations reveal that the mean secondary structure remains constant, but there are substantial differences in the intramolecular and intermolecular conformations upon single and double A2V mutation. Upon single mutation, the intrinsic disorder is reduced, the intermolecular potential energies are reduced, the population of intramolecular three-stranded beta-sheets is increased, and the number of all a dimer topologies is decreased. Taken together, these results offer an explanation for the reduced aggregation rate of the A beta 1-40 A2V-WT peptides and the protective effect of A2V in heterozygotes.}, issn = {1948-7193}, doi = {10.1021/acschemneuro.6b00053}, author = {Phuong Hoang Nguyen and Fabio Sterpone and Campanera, Josep M. and Nasica-Labouze, Jessica and Philippe Derreumaux} } @article {2016|1711, title = {In silico structural characterization of protein targets for drug development against Trypanosoma cruzi}, journal = {J. Mol. Model.}, volume = {22}, number = {10}, year = {2016}, month = {oct}, abstract = {Trypanosoma cruzi is the protozoan pathogen responsible for Chagas disease, which is a major public health problem in tropical and subtropical regions of developing countries and particularly in Brazil. Despite many studies, there is no efficient treatment against Chagas disease, and the search for new therapeutic targets specific to T. cruzi is critical for drug development. Here, we have revisited 41 protein sequences proposed by the analogous enzyme pipeline, and found that it is possible to provide structures for T. cruzi sequences with clear homologs or analogs in H. sapiens and likely associated with trypanothione reductase, cysteine synthase, and ATPase functions, and structures for sequences specific to T. cruzi and absent in H. sapiens associated with 2,4-dienoyl-CoA reductase, and leishmanolysin activities. The implications of our structures refined by atomistic molecular dynamics (monomer or dimer states) in their in vitro environments (aqueous solution or membrane bilayers) are discussed for drug development and suggest that all protein targets, except cysteine synthase, merit further investigation.}, issn = {1610-2940}, doi = {10.1007/s00894-016-3115-9}, author = {Lima, Carlyle Ribeiro and Carels, Nicolas and Ramos Guimaraes, Ana Carolina and Pierre Tuffery and Philippe Derreumaux} } @article {2016|1703, title = {Lattice model for amyloid peptides: OPEP force field parametrization and applications to the nucleus size of Alzheimer{\textquoteright}s peptides}, journal = {J. Chem. Phys.}, volume = {144}, number = {20}, year = {2016}, month = {may}, abstract = {Coarse-grained protein lattice models approximate atomistic details and keep the essential interactions. They are, therefore, suitable for capturing generic features of protein folding and amyloid formation at low computational cost. As our aim is to study the critical nucleus sizes of two experimentally well-characterized peptide fragments A beta(16-22) and A beta(37-42) of the full length A beta(1-42) Alzheimer{\textquoteright}s peptide, it is important that simulations with the lattice model reproduce all-atom simulations. In this study, we present a comprehensive force field parameterization based on the OPEP (Optimized Potential for Efficient protein structure Prediction) force field for an on-lattice protein model, which incorporates explicitly the formation of hydrogen bonds and directions of side-chains. Our bottom-up approach starts with the determination of the best lattice force parameters for the A beta(16-22) dimer by fitting its equilibrium parallel and anti-parallel beta-sheet populations to all-atom simulation results. Surprisingly, the calibrated force field is transferable to the trimer of A beta(16-22) and the dimer and trimer of A beta(37-42). Encouraged by this finding, we characterized the free energy landscapes of the two decamers. The dominant structure of the A beta(16-22) decamer matches the microcrystal structure. Pushing the simulations for aggregates between 4-mer and 12-mer suggests a nucleus size for fibril formation of 10 chains. In contrast, the A beta(37-42) decamer is largely disordered with mixed by parallel and antiparallel chains, suggesting that the nucleus size is >10 peptides. Our refined force field coupled to this on-lattice model should provide useful insights into the critical nucleation number associated with neurodegenerative diseases. Published by AIP Publishing.}, issn = {0021-9606}, doi = {10.1063/1.4951739}, author = {Thanh-Thuy Tran and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2016|1639, title = {MP2 and DFT studies of beta-D-neocarrabiose and beta-D-neocarrabiose monohydrate}, journal = {Comput. Theor. Chem.}, volume = {1091}, year = {2016}, month = {sep}, pages = {24{\textendash}30}, abstract = {MP2 and density functional theory calculations have been carried out on beta-D-neocarrabiose and its mono hydrate in order to determine the conformational preferences of these molecules in the gas phase and in solvent. Relaxed iso-energetic maps were first obtained using B3LYP/6-31G(d). Then, the lower energy conformers were further fully optimized using B3LYP, B3PW91 and MP2 methods. Overall, it was demonstrated that a lower energy conformer corresponding to the couple of dihedral angles (Phi,Psi)= (69 degrees,-117 degrees) is detected either in the gas phase or in solvent provided that full optimizations are performed on the conformers corresponding to the minima detected from the iso-energetic maps. (C) 2016 Elsevier B.V. All rights reserved.}, issn = {2210-271X}, doi = {10.1016/j.comptc.2016.07.009}, author = {Bestaoui-Berrekhchi-Berrahma, N. and Sekkal-Rahal, M. and Philippe Derreumaux and Yousfi, N.} } @article {2016|1735, title = {Multiscale simulation of molecular processes in cellular environments}, journal = {Philosophical Transactions of the Royal Society A-mathematical Physical and Engineering Sciences}, volume = {374}, number = {2080}, year = {2016}, abstract = {We describe the recent advances in studying biological systems via multiscale simulations. Our scheme is based on a coarse-grained representation of the macromolecules and a mesoscopic description of the solvent. The dual technique handles particles, the aqueous solvent and their mutual exchange of forces resulting in a stable and accurate methodology allowing biosystems of unprecedented size to be simulated. This article is part of the themed issue {\textquoteleft}Multiscale modelling at the physics-chemistry-biology interface{\textquoteright}.}, issn = {1364-503X}, doi = {10.1098/rsta.2016.0225}, author = {Chiricotto, Mara and Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2016|1703, title = {Nonequilibrium all-atom molecular dynamics simulation of the bubble cavitation and application to dissociate amyloid fibrils}, journal = {J. Chem. Phys.}, volume = {145}, number = {17}, year = {2016}, month = {nov}, abstract = {The cavitation of gas bubbles in liquids has been applied to different disciplines in life and natural sciences, and in technologies. To obtain an appropriate theoretical description of effects induced by the bubble cavitation, we develop an all-atom nonequilibrium molecular-dynamics simulation method to simulate bubbles undergoing harmonic oscillation in size. This allows us to understand the mechanism of the bubble cavitation-induced liquid shear stress on surrounding objects. The method is then employed to simulate an A beta fibril model in the presence of bubbles, and the results show that the bubble expansion and contraction exert water pressure on the fibril. This yields to the deceleration and acceleration of the fibril kinetic energy, facilitating the conformational transition between local free energy minima, and leading to the dissociation of the fibril. Our work, which is a proof-of-concept, may open a new, efficient way to dissociate amyloid fibrils using the bubble cavitation technique, and new venues to investigate the complex phenomena associated with amyloidogenesis. Published by AIP Publishing.}, issn = {0021-9606}, doi = {10.1063/1.4966263}, author = {Man Hoang Viet and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2016|1750, title = {Non-equivalent binding sites for Abeta1-40 on PrP determine the oligomerisation pathway}, journal = {Prion}, volume = {10}, number = {1}, year = {2016}, pages = {S40}, issn = {1933-6896}, author = {Grznarova, Katarina and Torrent, Joan and Munoz-Montesino, Carola and Nasica, Jessica and Philippe Derreumaux and Beringue, Vincent and Deslys, Jean-Philippe and Rezaei, Human} } @article {2016|1672, title = {A Novel Bifunctional Alkylphenol Anesthetic Allows Characterization of gamma-Aminobutyric Acid, Type A (GABAA), Receptor Subunit Binding Selectivity in Synaptosomes.}, journal = {J. Biol. Chem}, volume = {291}, year = {2016}, month = {sep}, pages = {20473{\textendash}86}, abstract = {

Propofol, an intravenous anesthetic, is a positive modulator of the GABAA receptor, but the mechanistic details, including the relevant binding sites and alternative targets, remain disputed. Here we undertook an in-depth study of alkylphenol-based anesthetic binding to synaptic membranes. We designed, synthesized, and characterized a chemically active alkylphenol anesthetic (2-((prop-2-yn-1-yloxy)methyl)-5-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenol, AziPm-click (1)), for affinity-based protein profiling (ABPP) of propofol-binding proteins in their native state within mouse synaptosomes. The ABPP strategy captured approximately 4\% of the synaptosomal proteome, including the unbiased capture of five alpha or beta GABAA receptor subunits. Lack of gamma2 subunit capture was not due to low abundance. Consistent with this, independent molecular dynamics simulations with alchemical free energy perturbation calculations predicted selective propofol binding to interfacial sites, with higher affinities for alpha/beta than gamma-containing interfaces. The simulations indicated hydrogen bonding is a key component leading to propofol-selective binding within GABAA receptor subunit interfaces, with stable hydrogen bonds observed between propofol and alpha/beta cavity residues but not gamma cavity residues. We confirmed this by introducing a hydrogen bond-null propofol analogue as a protecting ligand for targeted-ABPP and observed a lack of GABAA receptor subunit protection. This investigation demonstrates striking interfacial GABAA receptor subunit selectivity in the native milieu, suggesting that asymmetric occupancy of heteropentameric ion channels by alkylphenol-based anesthetics is sufficient to induce modulation of activity.

}, keywords = {anesthesia, anesthetic, click chemistry, GABA receptor, photoaffinity labeling}, doi = {10.1074/jbc.M116.736975}, author = {Woll, Kellie A. and Murlidaran, Sruthi and Pinch, Benika J. and J{\'e}r{\^o}me H{\'e}nin and Wang, Xiaoshi and Salari, Reza and Covarrubias, Manuel and Dailey, William P. and Grace Brannigan and Garcia, Benjamin A. and Roderic G Eckenhoff} } @article {2016|1733, title = {PEP-FOLD3: faster denovo structure prediction for linear peptides in solution and in complex}, journal = {Nucleic Acids Res.}, volume = {44}, number = {W1}, year = {2016}, pages = {W449-W454}, abstract = {Structure determination of linear peptides of 5-50 amino acids in aqueous solution and interacting with proteins is a key aspect in structural biology. PEP-FOLD3 is a novel computational framework, that allows both (i) de novo free or biased prediction for linear peptides between 5 and 50 amino acids, and (ii) the generation of native-like conformations of peptides interacting with a protein when the interaction site is known in advance. PEP-FOLD3 is fast, and usually returns solutions in a few minutes. Testing PEP-FOLD3 on 56 peptides in aqueous solution led to experimental-like conformations for 80\% of the targets. Using a benchmark of 61 peptide-protein targets starting from the unbound form of the protein receptor, PEP-FOLD3 was able to generate peptide poses deviating on average by 3.3 angstrom from the experimental conformation and return a native-like pose in the first 10 clusters for 52\% of the targets. PEP-FOLD3 is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD3.}, issn = {0305-1048}, doi = {10.1093/nar/gkw329}, author = {Lamiable, Alexis and Thevenet, Pierre and Rey, Julien and Vavrusa, Marek and Philippe Derreumaux and Pierre Tuffery} } @article {2016|1744, title = {Picosecond infrared laser-induced all-atom nonequilibrium molecular dynamics simulation of dissociation of viruses}, journal = {Phys. Chem. Chem. Phys.}, volume = {18}, number = {17}, year = {2016}, month = {may}, pages = {11951{\textendash}11958}, abstract = {Since the discovery of the plant pathogen tobacco mosaic virus as the first viral entity in the late 1800s, viruses traditionally have been mainly thought of as pathogens for disease-resistances. However, viruses have recently been exploited as nanoplatforms with applications in biomedicine and materials science. To this aim, a large majority of current methods and tools have been developed to improve the physical stability of viral particles, which may be critical to the extreme physical or chemical conditions that viruses may encounter during purification, fabrication processes, storage and use. However, considerably fewer studies are devoted to developing efficient methods to degrade or recycle such enhanced stability biomaterials. With this in mind, we carry out all-atom nonequilibriummolecular dynamics simulation, inspired by the recently developed mid-infrared free-electron laser pulse technology, to dissociate viruses. Adopting the poliovirus as a representative example, we find that the primary step in the dissociation process is due to the strong resonance between the amide I vibrational modes of the virus and the tuned laser frequencies. This process is determined by a balance between the formation and dissociation of the protein shell, reflecting the highly plasticity of the virus. Furthermore, our method should provide a feasible approach to simulate viruses, which is otherwise too expensive for conventional equilibrium all-atom simulations of such very large systems. Our work shows a proof of concept which may open a new, efficient way to cleave or to recycle virus-based materials, provide an extremely valuable tool for elucidating mechanical aspects of viruses, and may well play an important role in future fighting against virus-related diseases.}, issn = {1463-9076}, doi = {10.1039/c5cp07711g}, author = {Viet Hoang Man and Van-Oanh, Nguyen-Thi and Philippe Derreumaux and Li, Mai Suan and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2016|1550, title = {{S}ites of {A}nesthetic {I}nhibitory {A}ction on a {C}ationic {L}igand-{G}ated {I}on {C}hannel}, journal = {Structure}, volume = {24a}, number = {4}, year = {2016}, month = {apr}, pages = {595{\textendash}605}, author = {Laurent, B. and Murail, S. and Shahsavar, A. and Sauguet, L. and Delarue, M. and Marc Baaden} } @conference {2016|1608, title = {Toward Microscopic Simulations of Proteins in Cell-Like Environments}, booktitle = {Biophys. J.}, volume = {110}, number = {3, 1}, year = {2016}, note = {60th Annual Meeting of the Biophysical-Society, Los Angeles, CA, FEB 27-MAR 02, 2016}, month = {feb}, pages = {386A}, publisher = {Biophys Soc}, organization = {Biophys Soc}, issn = {0006-3495}, author = {Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2015|1716, title = {Ab initio RNA folding}, journal = {Journal of Physics-condensed Matter}, volume = {27}, number = {23}, year = {2015}, month = {jun}, pages = {233102}, doi = {10.1088/0953-8984/27/23/233102}, author = {Cragnolini, Tristan and Philippe Derreumaux and Pasquali, Samuela} } @article {2015|1634, title = {Amyloid beta Protein and Alzheimer{\textquoteright}s Disease: When Computer Simulations Complement Experimental Studies}, journal = {Chem. Rev.}, volume = {115}, number = {9}, year = {2015}, month = {may}, pages = {3518{\textendash}3563}, doi = {10.1021/cr500638n}, author = {Nasica-Labouze, Jessica and Phuong Hoang Nguyen and Fabio Sterpone and Berthoumieu, Olivia and Buchete, Nicolae-Viorel and Cote, Sebastien and De Simone, Alfonso and Doig, Andrew J. and Faller, Peter and Garcia, Angel and Laio, Alessandro and Li, Mai Suan and Melchionna, Simone and Mousseau, Normand and Mu, Yuguang and Paravastu, Anant and Pasquali, Samuela and Rosenman, David J. and Strodel, Birgit and Tarus, Bogdan and Viles, John H. and Zhang, Tong and Wang, Chunyu and Philippe Derreumaux} } @article {2015|1910, title = {Are coarse-grained models apt to detect protein thermal stability? The case of \{OPEP\} force field}, journal = {J. Non-cryst. Solids}, volume = {407}, year = {2015}, note = {7th IDMRCS: Relaxation in Complex Systems}, pages = {494{\textendash}501}, keywords = {Conformational substates network}, doi = {10.1016/j.jnoncrysol.2014.07.005}, url = {http://www.sciencedirect.com/science/article/pii/S0022309314002889}, author = {Maria Kalimeri and Philippe Derreumaux and Fabio Sterpone} } @article {2015|1708, title = {Coarse-Grained HiRE-RNA Model for ab Initio RNA Folding beyond Simple Molecules, Including Noncanonical and Multiple Base Pairings}, journal = {J. Chem. Theory Comput.}, volume = {11}, number = {7}, year = {2015}, pages = {3510{\textendash}3522}, doi = {10.1021/acs.jctc.5b00200}, author = {Cragnolini, Tristan and Laurin, Yoann and Philippe Derreumaux and Pasquali, Samuela} } @article {2015|1635, title = {Combined Experimental and Simulation Studies Suggest a Revised Mode of Action of the Anti-Alzheimer Disease Drug NQ-Trp}, journal = {Chemistry-a European Journal}, volume = {21}, number = {36}, year = {2015}, pages = {12657{\textendash}12666}, doi = {10.1002/chem.201500888}, author = {Berthoumieu, Olivia and Phuong Hoang Nguyen and del Castillo-Frias, Maria P. and Ferre, Sabrina and Tarus, Bogdan and Nasica-Labouze, Jessica and Noel, Sabrina and Saurel, Olivier and Rampon, Claire and Doig, Andrew J. and Philippe Derreumaux and Faller, Peter} } @article {2015|1768, title = {Communication: Multiple atomistic force fields in a single enhanced sampling simulation.}, journal = {The Journal of Chemical Physics}, volume = {143}, number = {2}, year = {2015}, month = {jul}, pages = {021101{\textendash}021101}, doi = {10.1063/1.4926535}, author = {Hoang Viet, Man and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2015|1704, title = {Communication: Multiple atomistic force fields in a single enhanced sampling simulation}, journal = {J. Chem. Phys.}, volume = {143}, number = {2}, year = {2015}, month = {jul}, pages = {021101}, doi = {10.1063/1.4926535}, author = {Man Hoang Viet and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2015|1679, title = {Conformational ensembles and sampled landscapes: analysis and comparison}, journal = {J. Comp. Chem.}, volume = {36}, year = {2015}, pages = {1213{\textendash}31}, author = {Fr{\'e}d{\'e}ric Cazals and A Roth and T Dreyfus and D Mazauric and Charles H. Robert} } @article {2015|1780, title = {{E}pock: rapid analysis of protein pocket dynamics}, journal = {Bioinformatics}, volume = {31}, number = {9}, year = {2015}, month = {may}, pages = {1478{\textendash}1480}, doi = {10.1093/bioinformatics/btu822}, author = {Laurent, Benoist and Matthieu Chavent and Cragnolini, Tristan and Dahl, Anna Caroline E. and Pasquali, Samuela and Philippe Derreumaux and Sansom, Mark S. P. and Marc Baaden} } @article {2015|1713, title = {Folding Atomistic Proteins in Explicit Solvent Using Simulated Tempering}, journal = {J. Phys. Chem. B}, volume = {119}, number = {23}, year = {2015}, month = {jun}, pages = {6941{\textendash}6951}, author = {Zhang, Tong and Phuong Hoang Nguyen and Nasica-Labouze, Jessica and Mu, Yuguang and Philippe Derreumaux} } @article {2015|1643, title = {Inhibition of protein aggregation and amyloid formation by small molecules}, journal = {Curr. Opin. Struct. Biol.}, volume = {30}, year = {2015}, month = {feb}, pages = {50{\textendash}56}, doi = {10.1016/j.sbi.2014.12.004}, author = {Doig, Andrew J. and Philippe Derreumaux} } @article {2015|1731, title = {Integrating multi-scale data on homologous recombination into a new recognition mechanism based on simulations of the RecA-ssDNA/dsDNA structure}, journal = {Nucleic Acids Res.}, volume = {43}, year = {2015}, month = {dec}, pages = {10251{\textendash}63}, abstract = {

RecA protein is the prototypical recombinase. Members of the recombinase family can accurately repair double strand breaks in DNA. They also provide crucial links between pairs of sister chromatids in eukaryotic meiosis. A very broad outline of how these proteins align homologous sequences and promote DNA strand exchange has long been known, as are the crystal structures of the RecA-DNA pre- and postsynaptic complexes; however, little is known about the homology searching conformations and the details of how DNA in bacterial genomes is rapidly searched until homologous alignment is achieved. By integrating a physical model of recognition to new modeling work based on docking exploration and molecular dynamics simulation, we present a detailed structure/function model of homology recognition that reconciles extremely quick searching with the efficient and stringent formation of stable strand exchange products and which is consistent with a vast body of previously unexplained experimental results.

}, doi = {10.1093/nar/gkv883}, author = {Yang, Darren and Boyer, Benjamin and Chantal Pr{\'e}vost and Danilowicz, Claudia and Prentiss, Mara} } @article {2015|1975, title = {{A}llosteric and hyperekplexic mutant phenotypes investigated on an α1 glycine receptor transmembrane structure}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {112}, number = {9}, year = {2015}, month = {mar}, pages = {2865{\textendash}2870}, author = {Moraga-Cid, G. and Sauguet, L. and Huon, C. and Malherbe, L. and Girard-Blanc, C. and Petres, S. and Murail, S. and Antoine Taly and Marc Baaden and Delarue, M. and Corringer, P. J.} } @article {2015|1664, title = {Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory.}, journal = {J. Membr. Biol.}, volume = {248}, year = {2015}, publisher = {Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, 11527, Athens, Greece, zcournia@bioacademy.gr.}, chapter = {611}, abstract = {

Membrane proteins mediate processes that are fundamental for the flourishing of biological cells. Membrane-embedded transporters move ions and larger solutes across membranes; receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. We present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function, and dynamics of membrane proteins.

}, doi = {10.1007/s00232-015-9802-0}, author = {Cournia, Zoe and Allen, Toby W. and Andricioaei, Ioan and Antonny, Bruno and Baum, Daniel and Grace Brannigan and Buchete, Nicolae-Viorel and Deckman, Jason T. and Delemotte, Lucie and Del Val, Coral and Friedman, Ran and Gkeka, Paraskevi and Hege, Hans-Christian and J{\'e}r{\^o}me H{\'e}nin and Kasimova, Marina A. and Kolocouris, Antonios and Michael L Klein and Khalid, Syma and Lemieux, M Joanne and Lindow, Norbert and Roy, Mahua and Selent, Jana and Mounir Tarek and Tofoleanu, Florentina and Vanni, Stefano and Urban, Sinisa and Wales, David J. and Smith, Jeremy C. and Bondar, Ana-Nicoleta} } @article {2015|1646, title = {Molecular structure of the NQTrp inhibitor with the Alzheimer A beta 1-28 monomer}, journal = {Eur. J. Med. Chem.}, volume = {91}, year = {2015}, month = {feb}, pages = {43{\textendash}50}, doi = {10.1016/j.ejmech.2014.07.002}, author = {Tarus, Bogdan and Phuong Hoang Nguyen and Berthoumieu, Olivia and Faller, Peter and Doig, Andrew J. and Philippe Derreumaux} } @article {2015|1449, title = {{P}redicting and exploring complex nucleic acids architectures through a coarse-grained model}, journal = {J. Biomol. Struct. Dyn.}, volume = {33 Suppl 1}, year = {2015}, pages = {30{\textendash}31}, author = {Cragnolini, T. and Doutreligne, S. and Marc Baaden and Philippe Derreumaux and Pasquali, S.} } @article {2015|1705, title = {Picosecond dissociation of amyloid fibrils with infrared laser: A nonequilibrium simulation study}, journal = {J. Chem. Phys.}, volume = {143}, number = {15}, year = {2015}, month = {oct}, pages = {155101}, doi = {10.1063/1.4933207}, author = {Man Hoang Viet and Philippe Derreumaux and Mai Suan Li and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2015|1745, title = {Picosecond melting of peptide nanotubes using an infrared laser: a nonequilibrium simulation study}, journal = {Phys. Chem. Chem. Phys.}, volume = {17}, number = {41}, year = {2015}, pages = {27275{\textendash}27280}, doi = {10.1039/c5cp04401d}, author = {Viet, Man Hoang and Phan Minh Truong and Philippe Derreumaux and Li, Mai Suan and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2015|1732, title = {The poor homology stringency in the heteroduplex allows strand exchange to incorporate desirable mismatches without sacrificing recognition in vivo}, journal = {Nucleic Acids Res.}, volume = {43}, year = {2015}, month = {jul}, pages = {6473{\textendash}85}, abstract = {

RecA family proteins are responsible for homology search and strand exchange. In bacteria, homology search begins after RecA binds an initiating single-stranded DNA (ssDNA) in the primary DNA-binding site, forming the presynaptic filament. Once the filament is formed, it interrogates double-stranded DNA (dsDNA). During the interrogation, bases in the dsDNA attempt to form Watson-Crick bonds with the corresponding bases in the initiating strand. Mismatch dependent instability in the base pairing in the heteroduplex strand exchange product could provide stringent recognition; however, we present experimental and theoretical results suggesting that the heteroduplex stability is insensitive to mismatches. We also present data suggesting that an initial homology test of 8 contiguous bases rejects most interactions containing more than 1/8 mismatches without forming a detectable 20 bp product. We propose that, in vivo, the sparsity of accidental sequence matches allows an initial 8 bp test to rapidly reject almost all non-homologous sequences. We speculate that once the initial test is passed, the mismatch insensitive binding in the heteroduplex allows short mismatched regions to be incorporated in otherwise homologous strand exchange products even though sequences with less homology are eventually rejected.

}, doi = {10.1093/nar/gkv610}, author = {Danilowicz, Claudia and Yang, Darren and Kelley, Craig and Chantal Pr{\'e}vost and Prentiss, Mara} } @article {2015|1701, title = {Predicting and exploring complex nucleic acids architectures through a coarse-grained model}, journal = {Journal of Biomolecular Structure \& Dynamics}, volume = {33}, year = {2015}, pages = {30{\textendash}31}, doi = {10.1080/07391102.2015.1032593}, author = {Cragnolini, T. and Doutreligne, S. and Marc Baaden and Philippe Derreumaux and Pasquali, S.} } @article {2015|1709, title = {Protein Simulations in Fluids: Coupling the OPEP Coarse-Grained Force Field with Hydrodynamics}, journal = {J. Chem. Theory Comput.}, volume = {11}, number = {4}, year = {2015}, month = {apr}, pages = {1843{\textendash}1853}, doi = {10.1021/ct501015h}, author = {Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2015|1727, title = {Replica-exchange molecular dynamics simulation for understanding the initial process of amyloid peptide aggregation}, journal = {Mol. Simul.}, volume = {41}, number = {10-12}, year = {2015}, month = {aug}, pages = {1041{\textendash}1044}, author = {Nishikawa, Naohiro and Phuong Hoang Nguyen and Philippe Derreumaux and Okamoto, Yuko} } @article {2015|1641, title = {Structure/function relationships in RecA protein-mediated homology recognition and strand exchange}, journal = {Crit. Rev. Biochem. Mol. Biol.}, volume = {50}, year = {2015}, pages = {453{\textendash}76}, abstract = {RecA family proteins include RecA, Rad51, and Dmc1. These recombinases are responsible for homology search and strand exchange. Homology search and strand exchange occur during double-strand break repair and in eukaryotes during meiotic recombination. In bacteria, homology search begins when RecA binds an initiating single-stranded DNA (ssDNA) in the primary DNA-binding site to form the presynaptic filament. The filament is a right-handed helix, where the initiating strand is bound deep within the filament. Once the presynaptic filament is formed, it interrogates nearby double-stranded DNA (dsDNA) to find a homologous sequence; therefore, we provide a detailed discussion of structural features of the presynaptic filament that play important functional roles. The discussion includes many diagrams showing multiple filament turns. These diagrams illustrate interactions that are not evident in single turn structures. The first dsDNA interactions with the presynaptic filament are insensitive to mismatches. The mismatch insensitive interactions lead to dsDNA deformation that triggers a homology testing process governed by kinetics. The first homology test involves {\^a}ˆ{\textonequarter}8 bases. Almost all interactions are rejected by this initial rapid test, leading to a new cycle of homology testing. Interactions that pass the initial rapid test proceed to a slower testing stage. That slower stage induces nonhomologous dsDNA to reverse strand exchange and begin a new cycle of homology testing. In contrast, homologous dsDNA continues to extend the heteroduplex strand-exchange product until ATP hydrolysis makes strand exchange irreversible.}, keywords = {Double-strand break repair, meiosis, meiotic recombination, Rad51, recombinase}, doi = {10.3109/10409238.2015.1092943}, author = {Prentiss, Mara and Chantal Pr{\'e}vost and Danilowicz, Claudia} } @article {2015|1714, title = {Structures of the Alzheimer{\textquoteright}s Wild-Type A beta 1-40 Dimer from Atomistic Simulations}, journal = {J. Phys. Chem. B}, volume = {119}, number = {33}, year = {2015}, pages = {10478{\textendash}10487}, doi = {10.1021/acs.jpcb.5b05593}, author = {Tarus, Bogdan and Thanh-Thuy Tran and Nasica-Labouze, Jessica and Fabio Sterpone and Phuong Hoang Nguyen and Philippe Derreumaux} } @conference {2015|1555, title = {UnityMol: interactive and ludic visual manipulation of coarse-grained RNA and other biomolecules}, booktitle = {Virtual and Augmented Reality for Molecular Science (VARMS@IEEEVR), 2015 IEEE 1st International Workshop on}, year = {2015}, month = {mar}, pages = {1{\textendash}6}, keywords = {biomolecular systems, coarse-grained RNA, collaborative research applications, data visualisation, feature extracti, HireRNA physics engine, interactive systems, Ludic visual manipulation, molecular biophysics, RNA, software architecture, teaching, UnityMol framework}, author = {S. Doutreligne and C. Gageat and T. Cragnolini and Antoine Taly and S. Pasquali and Philippe Derreumaux and Marc Baaden} } @conference {2015|1609, title = {What Computational Methods can Teach us about the Alzheimer-Protective Nature of A2V-and A2T-Mutant Amyloid-Beta Oligomers}, booktitle = {Biophys. J.}, volume = {108}, number = {2}, year = {2015}, pages = {204A-204A}, author = {Nasica-Labouze, Jessica and Tarus, Bogdan and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2014|1888, title = {Amyloid oligomer structure characterization from simulations: A general method}, journal = {J. Chem. Phys.}, volume = {140}, number = {9}, year = {2014}, month = {mar}, pages = {094105}, doi = {10.1063/1.4866902}, author = {Phuong Hoang Nguyen and Li, Mai Suan and Philippe Derreumaux} } @article {2014|1380, title = {Atomic and Dynamic Insights into the Beneficial Effect of the 1,4-Naphthoquinon-2-yl-L-tryptophan Inhibitor on Alzheimer{\textquoteright}s A beta 1-42 Dimer in Terms of Aggregation and Toxicity}, journal = {Acs Chem. Neurosci.}, volume = {5}, number = {2}, year = {2014}, month = {feb}, pages = {148{\textendash}159}, author = {Zhang, Tong and Xu, Weixin and Mu, Yuguang and Philippe Derreumaux} } @conference {2014|1784, title = {Coarse-Grain RNA Folding: Towards More Complex Structures}, booktitle = {Biophys. J.}, volume = {106}, number = {2, 1}, year = {2014}, note = {58th Annual Meeting of the Biophysical-Society, San Francisco, CA, FEB 15-19, 2014}, month = {jan}, pages = {283A}, author = {Cragnolini, Tristan and Laurin, Yoann and Philippe Derreumaux and Pasquali, Samuela} } @article {2014|1412, title = {{E}xa{V}iz: a flexible framework to analyse, steer and interact with molecular dynamics simulations}, journal = {Faraday Discuss.}, volume = {169}, year = {2014}, note = {[DOI:\href{http://dx.doi.org/10.1039/c3fd00142c}{10.1039/c3fd00142c}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25340956}{25340956}]}, pages = {119{\textendash}142}, author = {Dreher, M and Prevoteau-Jonquet, J and Trellet, M and Piuzzi, M and Marc Baaden and Raffin, B and Nicolas F{\'e}rey and Robert, S and Limet, S.} } @article {2014|1379, title = {Effect of the English Familial Disease Mutation (H6R) on the Monomers and Dimers of A beta 40 and A beta 42}, journal = {Acs Chem. Neurosci.}, volume = {5}, number = {8}, year = {2014}, month = {aug}, pages = {646{\textendash}657}, author = {Man Hoang Viet and Phuong Hoang Nguyen and Philippe Derreumaux and Li, Mai Suan} } @article {2014|1927, title = {Familial Alzheimer A2 V Mutation Reduces the Intrinsic Disorder and Completely Changes the Free Energy Landscape of the A beta 1-28 Monomer}, journal = {J. Phys. Chem. B}, volume = {118}, number = {2}, year = {2014}, month = {jan}, pages = {501{\textendash}510}, doi = {10.1021/jp4115404}, author = {Phuong Hoang Nguyen and Tarus, Bogdan and Philippe Derreumaux} } @article {2014|1411, title = {{I}nnovative interactive flexible docking method for multi-scale reconstruction elucidates dystrophin molecular assembly}, journal = {Faraday Discuss.}, volume = {169}, year = {2014}, note = {[DOI:\href{http://dx.doi.org/10.1039/c3fd00134b}{10.1039/c3fd00134b}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25340652}{25340652}]}, pages = {45{\textendash}62}, author = {Molza, A. E and Nicolas F{\'e}rey and Czjzek, M and Le Rumeur, E and Hubert, J. F and Tek, A and Laurent, B and Marc Baaden and Delalande, O.} } @article {2014|1893, title = {Improved PEP-FOLD Approach for Peptide and Miniprotein Structure Prediction}, journal = {J. Chem. Theory Comput.}, volume = {10}, number = {10}, year = {2014}, month = {oct}, pages = {4745{\textendash}4758}, doi = {10.1021/ct500592m}, author = {Shen, Yimin and Maupetit, Julien and Philippe Derreumaux and Pierre Tuffery} } @article {2014|1772, title = {INRIA Tech Report: Conformational ensembles and sampled landscapes: analysis and comparison.}, year = {2014}, author = {Fr{\'e}d{\'e}ric Cazals and T. Dreyfus and D. Mazauric and A. Roth and Charles H. Robert} } @article {2014|1798, title = {The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems}, journal = {Chem. Soc. Rev.}, volume = {43}, number = {13}, year = {2014}, pages = {4871{\textendash}4893}, doi = {10.1039/c4cs00048j}, author = {F. Sterpone and S. Melchionna and Pierre Tuffery and S. Pasquali and N. Mousseau and T. Cragnolini and Y Chebaro and J.-F. St-Pierre and M. Kalimeri and A. Barducci and Y. Laurin and A. Tek and Marc Baaden and Phuong Hoang Nguyen and Philippe Derreumaux} } @conference {2014|1760, title = {Optogating a powerful approach to control an ion-channel gate}, booktitle = {PURINERGIC SIGNALLING}, volume = {10}, number = {4}, year = {2014}, pages = {762{\textendash}762}, publisher = {SPRINGER VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS}, organization = {SPRINGER VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS}, author = {Lemoine, Damien and Habermacher, Chlo{\'e} and Martz, Adeline and M{\'e}ry, Pierre-Fran\c cois and Bouquier, Nathalie and Diverchy, Fanny and Antoine Taly and Rassendren, Fran\c cois and Specht, Alexandre and Grutter, Thomas} } @article {2014|1905, title = {Theoretical study of the NLO responses of some natural and unnatural amino acids used as probe molecules}, journal = {J. Mol. Model.}, volume = {20}, number = {8}, year = {2014}, month = {aug}, pages = {2388}, doi = {10.1007/s00894-014-2388-0}, author = {Derrar, S. N. and Sekkal-Rahal, M. and Philippe Derreumaux and Springborg, M.} } @article {2014, title = {Understanding Amyloid Fibril Nucleation and A beta Oligomer/Drug Interactions from Computer Simulations}, journal = {Acc. Chem. Res.}, volume = {47}, number = {2}, year = {2014}, pages = {603{\textendash}611}, author = {Nguyent, Phuong and Philippe Derreumaux} } @conference {2014|1496, title = {UnityMol: Interactive scientific visualization for integrative biology}, booktitle = {Large Data Analysis and Visualization (LDAV), 2014 IEEE 4th Symposium on}, year = {2014}, month = {nov}, pages = {109{\textendash}110}, keywords = {biology computing, biomolecular system visualization, data analysis, data exploration, data representation, data visualisation, information extraction, integrative biology, interactive scientific visualization, interactive virtual lab, molecular biophysics, UnityMol}, author = {S. Doutreligne and T. Cragnolini and S. Pasquali and Philippe Derreumaux and Marc Baaden} } @conference {2014|1783, title = {Wide Exploration of OPEP Protein Energy Landscapes using Advanced Monte Carlo Methods}, booktitle = {Biophys. J.}, volume = {106}, number = {2, 1}, year = {2014}, note = {58th Annual Meeting of the Biophysical-Society, San Francisco, CA, FEB 15-19, 2014}, month = {jan}, pages = {256A}, author = {Cragnolini, Tristan and Sutherland-Cash, Kyle H. and Wales, David and Pasquali, Samuela and Philippe Derreumaux} } @article {2013|1797, title = {Biomolecular hydration dynamics: a jump model perspective}, journal = {Chem. Soc. Rev.}, volume = {42}, number = {13}, year = {2013}, pages = {5672{\textendash}5683}, author = {Fogarty, Aoife C. and Elise Dubou{\'e}-Dijon and Sterpone, Fabio and Hynes, James T. and Laage, Damien} } @article {2013|1498, title = {coarse-grained models for protein folding ang aggregation}, journal = {Methods Mol. Biol.}, volume = {924}, year = {2013}, pages = {585{\textendash}600}, author = {Philippe Derreumaux} } @article {2013|1923, title = {Coarse-Grained Simulations of RNA and DNA Duplexes}, journal = {J. Phys. Chem. B}, volume = {117}, number = {27}, year = {2013}, month = {jul}, pages = {8047{\textendash}8060}, doi = {10.1021/jp400786b}, author = {Cragnolini, Tristan and Philippe Derreumaux and Pasquali, Samuela} } @article {2013|1887, title = {Communication: Simulated tempering with fast on-the-fly weight determination}, journal = {J. Chem. Phys.}, volume = {138}, number = {6}, year = {2013}, month = {feb}, pages = {061102}, doi = {10.1063/1.4792046}, author = {Phuong Hoang Nguyen and Okamoto, Yuko and Philippe Derreumaux} } @article {2013|1924, title = {Conformational Ensemble and Polymorphism of the All-Atom Alzheimer{\textquoteright}s A beta(37-42) Amyloid Peptide Oligomers}, journal = {J. Phys. Chem. B}, volume = {117}, number = {19}, year = {2013}, month = {may}, pages = {5831{\textendash}5840}, doi = {10.1021/jp401563n}, author = {Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2013|1904, title = {Density functional conformational study of 2-O-sulfated 3,6 anhydro-alpha-D-galactose and of neo-kappa- and iota-carrabiose molecules in gas phase and water}, journal = {J. Mol. Model.}, volume = {19}, number = {2}, year = {2013}, month = {feb}, pages = {893{\textendash}904}, doi = {10.1007/s00894-012-1621-y}, author = {Bestaoui-Berrekhchi-Berrahma, Noreya and Philippe Derreumaux and Sekkal-Rahal, Majda and Springborg, Michael and Sayede, Adlane and Yousfi, Noureddine and Kadoun, Abd-Ed-Daim} } @article {2013, title = {Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of A beta(40) and A beta(42)}, journal = {Acs Chem. Neurosci.}, volume = {4}, number = {11}, year = {2013}, month = {nov}, pages = {1446{\textendash}1457}, author = {Man Hoang Viet and Phuong Hoang Nguyen and Son Tung Ngo and Li, Mai Suan and Philippe Derreumaux} } @article {2013|1528, title = {{G}ame on, science - how video game technology may help biologists tackle visualization challenges}, journal = {Plos One}, volume = {8}, number = {3}, year = {2013}, pages = {e57990}, author = {Lv, Z. and Tek, A. and Da Silva, F. and Empereur-mot, C. and Matthieu Chavent and Marc Baaden} } @article {2013|1700, title = {Heme orientation modulates histidine dissociation and ligand binding kinetics in the hexacoordinated human neuroglobin}, journal = {J. Biol. Inorg. Chem.}, volume = {18}, number = {1}, year = {2013}, pages = {111{\textendash}122}, doi = {10.1007/s00775-012-0956-2}, author = {Bocahut, A. and Derrien, V. and Bernad, S. and Sebban, P. and S Sacquin-Mora and Guittet, E. and Lescop, E.} } @article {2013|1892, title = {Importance of the Ion-Pair Interactions in the OPEP Coarse-Grained Force Field: Parametrization and Validation}, journal = {J. Chem. Theory Comput.}, volume = {9}, number = {10}, year = {2013}, month = {oct}, pages = {4574{\textendash}4584}, doi = {10.1021/ct4003493}, author = {Sterpone, Fabio and Phuong Hoang Nguyen and Kalimeri, Maria and Philippe Derreumaux} } @article {2013|1531, title = {Interactive Molecular Dynamics: Scaling up to Large Systems.}, journal = {Procedia Comput. Sci.}, volume = {18}, year = {2013}, pages = {20{\textendash}29}, doi = {10.1016/j.procs.2013.05.165}, author = {M. Dreher and M. Piuzzi and A. Turki and Matthieu Chavent and Marc Baaden and Nicolas F{\'e}rey and S. Limet and B. Raffin and S. Robert} } @inbook {2013|1499, title = {Modeling macromolecular complexes: a journey across scales}, booktitle = {Modeling in Computational Biology and Biomedicine: A Multidisciplinary Endeavor}, year = {2013}, note = {(in press)}, publisher = {Springer-Verlag Berlin Heidelberg}, organization = {Springer-Verlag Berlin Heidelberg}, author = {Fr{\'e}d{\'e}ric Cazals and Tom Dreyfus and Charles H. Robert} } @article {2013|1925, title = {Molecular Mechanism of the Inhibition of EGCG on the Alzheimer A beta(1-42) Dimer}, journal = {J. Phys. Chem. B}, volume = {117}, number = {15}, year = {2013}, month = {apr}, pages = {3993{\textendash}4002}, doi = {10.1021/jp312573y}, author = {Zhang, Tong and Zhang, Jian and Philippe Derreumaux and Mu, Yuguang} } @article {2013|1973, title = {{O}ptical control of an ion channel gate}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {110}, number = {51}, year = {2013}, month = {dec}, pages = {20813{\textendash}20818}, author = {Lemoine, D. and Habermacher, C. and Martz, A. and Mery, P. F. and Bouquier, N. and Diverchy, F. and Antoine Taly and Rassendren, F. and Specht, A. and Grutter, T.} } @article {2013|1961, title = {Protein-protein interactions in a crowded environment: an analysis via cross-docking simulations and evolutionary information}, journal = {Plos Comput. Biol.}, volume = {9}, number = {12}, year = {2013}, month = {dec}, pages = {e1003369}, doi = {10.1371/journal.pcbi.1003369}, url = {http://hal.inria.fr/hal-00875116}, author = {Lopes, Anne and S Sacquin-Mora and Dimitrova, Viktoriya and Laine, Elodie and Ponty, Yann and Carbone, Alessandra} } @article {2013|1806, title = {Replica-exchange molecular dynamics simulations of the amyloid-beta(16-22) fragments}, journal = {European Biophysics Journal with Biophysics Letters}, volume = {42}, number = {1}, year = {2013}, note = {9th European-Biophysical-Societies-Association Congress, Lisbon, PORTUGAL, JUL 13-17, 2013}, month = {jul}, pages = {S68}, author = {Nishikawa, N. and Phuong Hoang Nguyen and Philippe Derreumaux and Okamoto, Y.} } @article {2013|1406, title = {{S}tructural basis for ion permeation mechanism in pentameric ligand-gated ion channels}, journal = {Embo J.}, volume = {32}, number = {5}, year = {2013}, month = {mar}, pages = {728{\textendash}741}, author = {Sauguet, L. and Poitevin, F. and Murail, S. and Van Renterghem, C. and Moraga-Cid, G. and Malherbe, L. and Thompson, A. W. and Koehl, P. and Corringer, P. J. and Marc Baaden and Delarue, M.} } @booklet {2013|1576, title = {Structural basis for ion permeation in a pentameric ligand-gated ion channel revealed by x-ray crystallograph}, year = {2013}, note = {44-45}, author = {Marc Baaden and M. Delarue} } @inbook {2012|1575, title = {Advances in Human-Protein Interaction - Interactive And Immersive Molecular Simulations}, year = {2012}, publisher = {Intech, Croatia}, organization = {Intech, Croatia}, chapter = {Protein Interaction / Book 2}, author = {A. Tek and B. Laurent and M. Piuzzi and Z. Lu and Marc Baaden and O. Delalande and Matthieu Chavent and Nicolas F{\'e}rey and C. Martin and L. Piccinali and B. Katz and P. Bourdot and Ludovic Autin}, editor = {W. Cai and H. Hong} } @article {2012|1920, title = {The Coarse-Grained OPEP Force Field for Non-Amyloid and Amyloid Proteins}, journal = {J. Phys. Chem. B}, volume = {116}, number = {30}, year = {2012}, month = {aug}, pages = {8741{\textendash}8752}, doi = {10.1021/jp301665f}, author = {Y Chebaro and Pasquali, Samuela and Philippe Derreumaux} } @article {2012|1955, title = {Configurational entropy: an improvement of the quasiharmonic approximation using configurational temperature}, journal = {Phys. Chem. Chem. Phys.}, volume = {14}, number = {20}, year = {2012}, pages = {877{\textendash}886}, doi = {10.1039/c1cp21779h}, author = {Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2012|1911, title = {Delivering the native structures of peptides from computer simulations and predicted NMR proton chemical shifts}, journal = {J. Pept. Sci.}, volume = {18}, number = {1}, year = {2012}, month = {sep}, pages = {S38}, author = {Thevenet, P. and Shen, Y. and Maupetit, J. and Guyon, F. and Padilla, A. and Philippe Derreumaux and Pierre Tuffery} } @article {2012|1922, title = {Distinct Dimerization for Various Alloforms of the Amyloid-Beta Protein: A beta(1-40), A beta(1-42), and A beta(1-40)(D23N)}, journal = {J. Phys. Chem. B}, volume = {116}, number = {13}, year = {2012}, month = {apr}, pages = {4043{\textendash}4055}, doi = {10.1021/jp2126366}, author = {Cote, Sebastien and Laghaei, Rozita and Philippe Derreumaux and Mousseau, Normand} } @article {2012|1932, title = {Flexibility and binding affinity in protein-ligand, protein-protein and multi-component protein interactions: limitations of current computational approaches}, journal = {Journal of the Royal Society Interface}, volume = {9}, number = {66}, year = {2012}, month = {jan}, pages = {20{\textendash}33}, doi = {10.1098/rsif.2011.0584}, author = {Pierre Tuffery and Philippe Derreumaux} } @article {2012|1756, title = {Involvement of the cysteine-rich head domain in activation and desensitization of the P2X1 receptor}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {28}, year = {2012}, pages = {11396{\textendash}11401}, publisher = {National Acad Sciences}, author = {L{\"o}rinczi, {\'E}va and Bhargava, Yogesh and Marino, Stephen F and Antoine Taly and Kaczmarek-H{\'a}jek, Karina and Barrantes-Freer, Alonso and Dutertre, S{\'e}bastien and Grutter, Thomas and Rettinger, J{\"u}rgen and Nicke, Annette} } @article {2012|1458, title = {Mixing atomistic and coarse grain solvation models for MD simulations: let WT4 handle the bulk}, journal = {Jctc}, year = {2012}, month = {jun}, doi = {10.1021/ct3001816}, author = {L. Darre and A. Tek and Marc Baaden and S. Pantano} } @article {2012|1546, title = {Modeling complex biological systems: From solution chemistry to membranes and channels}, journal = {Pure Appl. Chem.}, volume = {ASAP}, year = {2012}, month = {nov}, doi = {10.1351/PAC-CON-12-04-10}, author = {B. Laurent and S. Murail and F. Da Silva and P.-J. Corringer and Marc Baaden} } @article {2012|1506, title = {A novel Locally Closed Conformation of a Bacterial Pentameric Proton-gated Ion Channel}, journal = {Nature Structural \& Molecular Biology}, year = {2012}, month = {apr}, author = {M. Prevost and L. Sauguet and H. Nury and C. Van Renterghem and C. Huon and F. Poitevin and Marc Baaden and M. Delarue and P.-J. Corringer} } @article {2012|1944, title = {PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides}, journal = {Nucleic Acids Res.}, volume = {40}, number = {W1}, year = {2012}, month = {jul}, pages = {W288-W293}, doi = {10.1093/nar/gks419}, author = {Thevenet, Pierre and Shen, Yimin and Maupetit, Julien and Guyon, Frederic and Philippe Derreumaux and Pierre Tuffery} } @article {2012|1886, title = {Structural, thermodynamical, and dynamical properties of oligomers formed by the amyloid NNQQ peptide: Insights from coarse-grained simulations}, journal = {J. Chem. Phys.}, volume = {137}, number = {2}, year = {2012}, month = {jul}, pages = {025101}, doi = {10.1063/1.4732761}, author = {Lu, Yan and Wei, Guanghong and Philippe Derreumaux} } @article {2012|1921, title = {Structures of A beta 17-42 Trimers in Isolation and with Five Small-Molecule Drugs Using a Hierarchical Computational Procedure}, journal = {J. Phys. Chem. B}, volume = {116}, number = {29, SI}, year = {2012}, month = {jul}, pages = {8412{\textendash}8422}, doi = {10.1021/jp2118778}, author = {Y Chebaro and Jiang, Ping and Zang, Tong and Mu, Yuguang and Phuong Hoang Nguyen and Mousseau, Normand and Philippe Derreumaux} } @article {2012|1813, title = {Substitutions at residue 211 in the prion protein drive a switch between CJD and GSS syndrome, a new mechanism governing inherited neurodegenerative disorders}, journal = {Hum. Mol. Genet.}, volume = {21}, number = {26}, year = {2012}, month = {dec}, pages = {5417{\textendash}5428}, doi = {10.1093/hmg/dds377}, author = {Katell Peoc{\textquoteright}h and Etienne Levavasseur and Emilien Delmont and Alfonso De Simone Isabelle Laffont-Proust and Nicolas Privat and Y Chebaro and C{\'e}line Chapuis Pierre Bedoucha and Jean-Philippe Brandel and Annie Laquerriere and Jean-Louis Kemeny Jean-Jacques Hauw and Michel Borg and Human Rezaei and Philippe Derreumaux Jean-Louis Laplanche and St{\'e}phane Ha{\"\i}k} } @article {2012|2016, title = {{T}hermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics}, journal = {J. R. Soc. Interface}, volume = {9}, number = {76}, year = {2012}, month = {nov}, pages = {2845{\textendash}2855}, doi = {10.1098/rsif.2012.0364}, author = {Stadler, A. M. and Garvey, C. J. and Bocahut, A. and S Sacquin-Mora and Digel, I. and Schneider, G. J. and Natali, F. and Artmann, G. M. and Zaccai, G.} } @article {2012|1816, title = {Theoretical study on a series of push-pull molecules grafted on methacrylate copolymers serving for nonlinear optics}, journal = {Int. J. Quantum Chem.}, volume = {112}, number = {15}, year = {2012}, month = {aug}, pages = {2735{\textendash}2742}, doi = {10.1002/qua.23299}, author = {Derrar, S. N. and Sekkal-Rahal, M. and Guemra, K. and Philippe Derreumaux} } @article {2011|1891, title = {Assessing the Quality of the OPEP Coarse-Grained Force Field}, journal = {J. Chem. Theory Comput.}, volume = {7}, number = {6}, year = {2011}, month = {jun}, pages = {1928{\textendash}1934}, doi = {10.1021/ct100646f}, author = {Barducci, Alessandro and Bonomi, Massimiliano and Philippe Derreumaux} } @article {2011|1610, title = {Carbon Nanotube Inhibits the Formation of beta-Sheet-Rich Oligomers of the Alzheimer{\textquoteright}s Amyloid-beta(16-22) Peptide}, journal = {Biophys. J.}, volume = {101}, number = {9}, year = {2011}, month = {nov}, pages = {2267{\textendash}2276}, doi = {10.1016/j.bpj.2011.09.046}, author = {Li, Huiyu and Luo, Yin and Philippe Derreumaux and Wei, Guanghong} } @conference {2011|1611, title = {Characterization of the Aggregation Pathway for a 20-mer of GNNQQNY using Coarse-Grained and All-Atom Representations}, booktitle = {Biophys. J.}, volume = {100}, number = {3}, year = {2011}, month = {feb}, pages = {Biophys Soc}, author = {Nasica-Labouze, Jessica and Meli, Massimiliano and Philippe Derreumaux and Colombo, Giorgio and Mousseau, Normand} } @article {2011|1665, title = {Community-wide assessment of protein-interface modeling suggests improvements to design methodology.}, journal = {J. Mol. Biol.}, volume = {414}, year = {2011}, month = {nov}, pages = {289{\textendash}302}, abstract = {

The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community-wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting that there may be important physical chemistry missing in the energy calculations. A total of 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the nonpolar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were, on average, structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a nonbinder.

}, keywords = {Binding Sites, Models, Molecular, Protein Binding, Proteins}, issn = {1089-8638}, doi = {10.1016/j.jmb.2011.09.031}, author = {Fleishman, Sarel J and Whitehead, Timothy A and Strauch, Eva-Maria and Corn, Jacob E and Qin, Sanbo and Zhou, Huan-Xiang and Mitchell, Julie C and Demerdash, Omar N A and Takeda-Shitaka, Mayuko and Terashi, Genki and Moal, Iain H and Li, Xiaofan and Bates, Paul A and Martin Zacharias and Park, Hahnbeom and Ko, Jun-su and Lee, Hasup and Seok, Chaok and Bourquard, Thomas and Bernauer, Julie and Poupon, Anne and Az{\'e}, J{\'e}r{\^o}me and Soner, Seren and Ovali, Sefik Kerem and Ozbek, Pemra and Tal, Nir Ben and Haliloglu, T{\"u}rkan and Hwang, Howook and Vreven, Thom and Pierce, Brian G and Weng, Zhiping and P{\'e}rez-Cano, Laura and Pons, Carles and Fern{\'a}ndez-Recio, Juan and Jiang, Fan and Yang, Feng and Gong, Xinqi and Cao, Libin and Xu, Xianjin and Liu, Bin and Wang, Panwen and Li, Chunhua and Wang, Cunxin and Charles H. Robert and Guharoy, Mainak and Liu, Shiyong and Huang, Yangyu and Li, Lin and Guo, Dachuan and Chen, Ying and Xiao, Yi and London, Nir and Itzhaki, Zohar and Schueler-Furman, Ora and Inbar, Yuval and Potapov, Vladimir and Cohen, Mati and Schreiber, Gideon and Tsuchiya, Yuko and Kanamori, Eiji and Standley, Daron M and Nakamura, Haruki and Kinoshita, Kengo and Driggers, Camden M and Hall, Robert G and Morgan, Jessica L and Hsu, Victor L and Zhan, Jian and Yang, Yuedong and Zhou, Yaoqi and Kastritis, Panagiotis L and Bonvin, Alexandre M J J and Zhang, Weiyi and Camacho, Carlos J and Kilambi, Krishna P and Sircar, Aroop and Gray, Jeffrey J and Ohue, Masahito and Uchikoga, Nobuyuki and Matsuzaki, Yuri and Ishida, Takashi and Akiyama, Yutaka and Khashan, Raed and Bush, Stephen and Fouches, Denis and Tropsha, Alexander and Esquivel-Rodr{\'\i}guez, Juan and Kihara, Daisuke and Stranges, P Benjamin and Jacak, Ron and Kuhlman, Brian and Huang, Sheng-You and Zou, Xiaoqin and Wodak, Shoshana J and Janin, Jo{\"e}l and Baker, David} } @article {2011|1890, title = {Distinct Morphologies for Amyloid Beta Protein Monomer: A beta(1-40), A beta(1-42), and A beta(1-40)(D23N)}, journal = {J. Chem. Theory Comput.}, volume = {7}, number = {8}, year = {2011}, month = {aug}, pages = {2584{\textendash}2592}, doi = {10.1021/ct1006967}, author = {Cote, Sebastien and Philippe Derreumaux and Mousseau, Normand} } @article {2011|1953, title = {Effects of all-atom force fields on amyloid oligomerization: replica exchange molecular dynamics simulations of the A beta(16-22) dimer and trimer}, journal = {Phys. Chem. Chem. Phys.}, volume = {13}, number = {20}, year = {2011}, pages = {9778{\textendash}9788}, doi = {10.1039/c1cp20323a}, author = {Phuong Hoang Nguyen and Li, Mai Suan and Philippe Derreumaux} } @article {2011|1919, title = {Effects of G33A and G33I Mutations on the Structures of Monomer and Dimer of the Amyloid-beta Fragment 29-42 by Replica Exchange Molecular Dynamics Simulations}, journal = {J. Phys. Chem. B}, volume = {115}, number = {5}, year = {2011}, month = {feb}, pages = {1282{\textendash}1288}, doi = {10.1021/jp110269a}, author = {Lu, Yan and Wei, Guanghong and Philippe Derreumaux} } @article {2011|1432, title = {Electrostatically{\textendash}driven fast association and perdeuteration allow transferred cross{\textendash}relaxation detection for G protein{\textendash}coupled receptor ligands with equilibrium dissociation constants in the high{\textendash}to{\textendash}low nanomolar range}, journal = {J Biomolecular Nmr}, volume = {50}, number = {3}, year = {2011}, month = {jul}, pages = {191{\textendash}5}, url = {http://www.ibpc.fr/UMR7099/Publis/pdf/Catoire11.pdf}, author = {L. J. Catoire and M. Damian and Marc Baaden and E. Guittet and J.-L. Ban{\`e}res} } @article {2011|1612, title = {Enzyme Closure and Nucleotide Binding Structurally Lock Guanylate Kinase}, journal = {Biophys. J.}, volume = {101}, number = {6}, year = {2011}, pages = {1440{\textendash}1449}, doi = {10.1016/j.bpj.2011.07.048}, author = {Delalande, O. and S Sacquin-Mora and Marc Baaden} } @article {2011|1972, title = {{A}gonist trapped in {A}{T}{P}-binding sites of the {P}2{X}2 receptor}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {108}, number = {22}, year = {2011}, month = {may}, pages = {9066{\textendash}9071}, author = {Jiang, R. and Lemoine, D. and Martz, A. and Antoine Taly and Gonin, S. and Prado de Carvalho, L. and Specht, A. and Grutter, T.} } @article {2011|1889, title = {Impact of Thermostats on Folding and Aggregation Properties of Peptides Using the Optimized Potential for Efficient Structure Prediction Coarse-Grained Model}, journal = {J. Chem. Theory Comput.}, volume = {7}, number = {5}, year = {2011}, month = {may}, pages = {1502{\textendash}1510}, doi = {10.1021/ct100619p}, author = {Spill, Yannick G. and Pasquali, Samuela and Philippe Derreumaux} } @article {2011|1966, title = {Intrinsic Determinants of A beta(12-24) pH-Dependent Self-Assembly Revealed by Combined Computational and Experimental Studies}, journal = {Plos One}, volume = {6}, number = {9}, year = {2011}, month = {sep}, pages = {e24329}, doi = {10.1371/journal.pone.0024329}, author = {Xu, Weixin and Zhang, Ce and Philippe Derreumaux and Graslund, Astrid and Morozova-Roche, Ludmilla and Mu, Yuguang} } @article {2011|1962, title = {A Multiscale Approach to Characterize the Early Aggregation Steps of the Amyloid-Forming Peptide GNNQQNY from the Yeast Prion Sup-35}, journal = {Plos Comput. Biol.}, volume = {7}, number = {5}, year = {2011}, month = {may}, pages = {e1002051}, doi = {10.1371/journal.pcbi.1002051}, author = {Nasica-Labouze, Jessica and Meli, Massimiliano and Philippe Derreumaux and Colombo, Giorgio and Mousseau, Normand} } @article {2011|1738, title = {Non-monotonic dependence of water reorientation dynamics on surface hydrophilicity: competing effects of the hydration structure and hydrogen-bond strength}, journal = {Phys. Chem. Chem. Phys.}, volume = {13}, year = {2011}, pages = {19911}, abstract = {

The reorientation dynamics of interfacial water molecules was recently shown to change non-monotonically next to surfaces of increasing hydrophilicity, with slower dynamics next to strongly hydrophobic (apolar) and very hydrophilic surfaces, and faster dynamics next to surfaces of intermediate hydrophilicities. Through a combination of molecular dynamics simulations and analytic modeling, we provide a molecular interpretation of this behavior. We show that this non-monotonic dependence arises from two competing effects induced by the increasing surface hydrophilicity: first a change in the hydration structure with an enhanced population of water OH bonds pointing toward the surface and second a strengthening of the water-surface interaction energy. The extended jump model, including the effects due to transition-state excluded volume and transition-state hydrogen-bond strength, provides a quasi-quantitative description of the non-monotonic changes in the water reorientation dynamics with surface hydrophilicity.

}, issn = {1463-9076}, author = {Guillaume Stirnemann and Castrillon, Santiago Romero-Vargas and Hynes, James T. and Rossky, Peter J. and Debenedetti, Pablo G. and Laage, Damien} } @article {2011|1748, title = {Optimizing the design of oligonucleotides for homology directed gene targeting}, journal = {Plos One}, volume = {6}, year = {2011}, pages = {e14795}, abstract = {

BACKGROUND: Gene targeting depends on the ability of cells to use homologous recombination to integrate exogenous DNA into their own genome. A robust mechanistic model of homologous recombination is necessary to fully exploit gene targeting for therapeutic benefit. METHODOLOGY/PRINCIPAL FINDINGS: In this work, our recently developed numerical simulation model for homology search is employed to develop rules for the design of oligonucleotides used in gene targeting. A Metropolis Monte-Carlo algorithm is used to predict the pairing dynamics of an oligonucleotide with the target double-stranded DNA. The model calculates the base-alignment between a long, target double-stranded DNA and a probe nucleoprotein filament comprised of homologous recombination proteins (Rad51 or RecA) polymerized on a single strand DNA. In this study, we considered different sizes of oligonucleotides containing 1 or 3 base heterologies with the target; different positions on the probe were tested to investigate the effect of the mismatch position on the pairing dynamics and stability. We show that the optimal design is a compromise between the mean time to reach a perfect alignment between the two molecules and the stability of the complex. CONCLUSION AND SIGNIFICANCE: A single heterology can be placed anywhere without significantly affecting the stability of the triplex. In the case of three consecutive heterologies, our modeling recommends using long oligonucleotides (at least 35 bases) in which the heterologous sequences are positioned at an intermediate position. Oligonucleotides should not contain more than 10\% consecutive heterologies to guarantee a stable pairing with the target dsDNA. Theoretical modeling cannot replace experiments, but we believe that our model can considerably accelerate optimization of oligonucleotides for gene therapy by predicting their pairing dynamics with the target dsDNA.

}, doi = {10.1371/journal.pone.0014795}, author = {Min{\'e}-Hattab, Judith and Fleury, Genevi{\`e}ve and Chantal Pr{\'e}vost and Dutreix, Marie and Viovy, Jean-Louis} } @article {2011|1782, title = {Simulation of the Oligomerization Pathway for Different Alloforms of the Amyloid Beta Protein Related to Alzheimer{\textquoteright}s Disease}, journal = {Biophys. J.}, volume = {100}, number = {3, 1}, year = {2011}, note = {55th Annual Meeting of the Biophysical-Society, Baltimore, MD, MAR 05-09, 2011}, month = {feb}, pages = {401}, author = {Cote, Sebastien and Laghaei, Rozita and Philippe Derreumaux and Mousseau, Normand} } @article {2011|1505, title = {X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel}, journal = {Nature}, volume = {469}, year = {2011}, month = {jan}, pages = {428{\textendash}431}, keywords = {anaesthetics, desflurane, GLIC, propofol}, url = {http://www.nature.com/nature/journal/v469/n7330/full/nature09647.html}, author = {H. Nury and C. Van Renterghem and Y. Weng and A. Tran and Marc Baaden and V. Dufresne and J.-P. Changeux and J. M. Sonner and M. Delarue and P.-J. Corringer} } @article {2010|1865, title = {An atomistic model for simulations of the general anesthetic isoflurane}, journal = {J. Phys. Chem. B}, volume = {114}, number = {1}, year = {2010}, pages = {604{\textendash}612}, publisher = {Laboratoire d{\textquoteright}Ing{\'e}nierie des Syst{\`e}mes Macromol{\'e}culaires, CNRS, Marseille, France. jhenin@ifr88.cnrs-mrs.fr}, abstract = {An atomistic model of isoflurane is constructed and calibrated to describe its conformational preferences and intermolecular interactions. The model, which is compatible with the CHARMM force field for biomolecules, is based on target quantities including bulk liquid properties, molecular conformations, and local interactions with isolated water molecules. Reference data is obtained from tabulated thermodynamic properties and high-resolution structural information from gas-phase electron diffraction, as well as DFT calculations at the B3LYP level. The model is tested against experimentally known solvation properties in water and oil, and shows quantitative agreement. In particular, isoflurane is faithfully described as lipophilic, yet nonhydrophobic, a combination of properties critical to its pharmacological activity. Intermolecular interactions of the model are further probed through simulations of the binding of isoflurane to a binding site in horse spleen apoferritin (HSAF). The observed binding mode compares well with crystallographic data, and the calculated binding affinities are compatible with experimental results, although both computational and experimental measurements are challenging and provide results with limited precision. The model is expected to be useful for detailed simulations of the elementary molecular processes associated with anesthesia. Full parameters are provided as Supporting Information.}, doi = {10.1021/jp9088035}, author = {J{\'e}r{\^o}me H{\'e}nin and Grace Brannigan and William P Dailey and Roderic G Eckenhoff and Michael L Klein} } @article {2010|1918, title = {Effects of the RGTFEGKF Inhibitor on the Structures of the Transmembrane Fragment 70-86 of Glycophorin A: An All-Atom Molecular Dynamics Study}, journal = {J. Phys. Chem. B}, volume = {114}, number = {2}, year = {2010}, month = {jan}, pages = {1004{\textendash}1009}, doi = {10.1021/jp908889q}, author = {Li, Huiyu and Luo, Yin and Philippe Derreumaux and Wei, Guanghong} } @article {2010|1901, title = {A Fast Method for Large-Scale De Novo Peptide and Miniprotein Structure Prediction}, journal = {J. Comput. Chem.}, volume = {31}, number = {4}, year = {2010}, month = {mar}, pages = {726{\textendash}738}, doi = {10.1002/jcc.21365}, author = {Maupetit, Julien and Philippe Derreumaux and Pierre Tuffery} } @article {2010|1613, title = {Functional Modes and Residue Flexibility Control the Anisotropic Response of Guanylate Kinase to Mechanical Stress}, journal = {Biophys. J.}, volume = {99}, number = {10}, year = {2010}, pages = {3412{\textendash}3419}, doi = {10.1016/j.bpj.2010.09.026}, author = {S Sacquin-Mora and Delalande, O. and Marc Baaden} } @article {2010|1917, title = {HiRE-RNA: A High Resolution Coarse-Grained Energy Model for RNA}, journal = {J. Phys. Chem. B}, volume = {114}, number = {37}, year = {2010}, month = {sep}, pages = {11957{\textendash}11966}, doi = {10.1021/jp102497y}, author = {Pasquali, Samuela and Philippe Derreumaux} } @article {2010|1885, title = {Low molecular weight oligomers of amyloid peptides display beta-barrel conformations: A replica exchange molecular dynamics study in explicit solvent}, journal = {J. Chem. Phys.}, volume = {132}, number = {16}, year = {2010}, month = {apr}, pages = {165103}, doi = {10.1063/1.3385470}, author = {De Simone, Alfonso and Philippe Derreumaux} } @article {2010|1512, title = {{M}odeling the early stage of {D}{N}{A} sequence recognition within {R}ec{A} nucleoprotein filaments}, journal = {Nucleic Acids Res.}, volume = {38}, year = {2010}, month = {oct}, pages = {6313{\textendash}6323}, author = {A Saladin and Amourda, C. and Poulain, P. and Nicolas F{\'e}rey and Marc Baaden and Martin Zacharias and Delalande, O. and Chantal Pr{\'e}vost} } @article {2010|1516, title = {{M}ulti-resolution approach for interactively locating functionally linked ion binding sites by steering small molecules into electrostatic potential maps using a haptic device}, journal = {Pac. Symp. Biocomput.}, year = {2010}, pages = {205{\textendash}215}, author = {Delalande, O. and Nicolas F{\'e}rey and Laurent, B. and Gueroult, M. and Hartmann, B. and Marc Baaden} } @article {2010|1529, title = {{O}ne-microsecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {107}, year = {2010}, month = {apr}, pages = {6275{\textendash}6280}, author = {Nury, H. and Poitevin, F. and Van Renterghem, C. and Changeux, J. P. and Corringer, P. J. and Delarue, M. and Marc Baaden} } @article {2010|1395, title = {{P}hotocontrol of protein activity in cultured cells and zebrafish with one- and two-photon illumination}, journal = {Chembiochem}, volume = {11}, year = {2010}, month = {mar}, pages = {653{\textendash}663}, author = {Sinha, D. K. and Neveu, P. and Gagey, N. and Aujard, I. and Benbrahim-Bouzidi, C. and Le Saux, T. and Rampon, C. and Gauron, C. and Goetz, B. and Dubruille, S. and Marc Baaden and Volovitch, M. and Bensimon, D. and Vriz, S. and Jullien, L.} } @article {2010|2007, title = {{A} putative extracellular salt bridge at the subunit interface contributes to the ion channel function of the {A}{T}{P}-gated {P}2{X}2 receptor}, journal = {J. Biol. Chem.}, volume = {285}, number = {21}, year = {2010}, month = {may}, pages = {15805{\textendash}15815}, publisher = {American Society for Biochemistry and Molecular Biology}, author = {Jiang, R. and Martz, A. and Gonin, S. and Antoine Taly and de Carvalho, L. P. and Grutter, T.} } @article {2010|1789, title = {Single-spanning transmembrane domains in cell growth and cell-cell interactions: More than meets the eye?}, journal = {Cell Adh. Migr.}, volume = {4}, number = {2}, year = {2010}, month = {apr}, pages = {313{\textendash}324}, abstract = {

As a whole, integral membrane proteins represent about one third of sequenced genomes, and more than 50\% of currently available drugs target membrane proteins, often cell surface receptors. Some membrane protein classes, with a defined number of transmembrane (TM) helices, are receiving much attention because of their great functional and pharmacological importance, such as G protein-coupled receptors possessing 7 TM segments. Although they represent roughly half of all membrane proteins, bitopic proteins (with only 1 TM helix) have so far been less well characterized. Though they include many essential families of receptors, such as adhesion molecules and receptor tyrosine kinases, many of which are excellent targets for biopharmaceuticals (peptides, antibodies, et al.). A growing body of evidence suggests a major role for interactions between TM domains of these receptors in signaling, through homo and heteromeric associations, conformational changes, assembly of signaling platforms, etc. Significantly, mutations within single domains are frequent in human disease, such as cancer or developmental disorders. This review attempts to give an overview of current knowledge about these interactions, from structural data to therapeutic perspectives, focusing on bitopic proteins involved in cell signaling.

}, keywords = {Animals, Biological, Humans, Membrane Proteins, Models, Protein Structure, Secondary, Signal Transduction, Tertiary}, issn = {1933-6926}, doi = {10.4161/cam.4.2.12430}, author = {Pierre Hubert and Paul Sawma and Jean-Pierre Duneau and Jonathan Khao and J{\'e}r{\^o}me H{\'e}nin and Dominique Bagnard and James Sturgis} } @article {2010|1444, title = {{T}he molecular recognition mechanism for superoxide dismutase presequence binding to the mitochondrial protein import receptor {T}om20 from {O}ryza sativa involves an {L}{R}{T}{L}{A} motif}, journal = {J. Phys. Chem. B}, volume = {114}, year = {2010}, month = {nov}, pages = {13839{\textendash}13846}, author = {Y. Zhang and Marc Baaden and J. Yan and J. Shao and S. Qiu and Y. Wu and Y. Ding} } @article {2010|1457, title = {{A}tomic structure and dynamics of pentameric ligand-gated ion channels: new insight from bacterial homologues}, journal = {J. Physiol. (lond.)}, volume = {588}, year = {2010}, month = {feb}, pages = {565{\textendash}572}, author = {Corringer, P. J. and Marc Baaden and Bocquet, N. and Delarue, M. and Dufresne, V. and Nury, H. and Prevost, M. and Van Renterghem, C.} } @article {2010, title = {The VLITL aggregation-prone motif might trigger amyloid fibril formation of fibrinogen A alpha-chain frameshift variants in vivo}, journal = {Amyloid-journal of Protein Folding Disorders}, volume = {17}, number = {Suppl. 1}, year = {2010}, note = {12th International Symposium on Amyloidosis from Molecular Mechanisms Toward the Cure of Systemic Amyloidoses, Rome, ITALY, APR 18-21, 2010}, pages = {96{\textendash}97}, author = {Valleix, S. and Philippe Derreumaux and Garnier, C. and Briki, F. and Boimard, M. and Doucet, J. and Rioux-Leclercq, N. and Martin, L. and Grateau, G. and Delpech, M. and Le Pogamp, P.} } @article {2009|1399, title = {{C}oarse-grain simulations of the {R}-{S}{N}{A}{R}{E} fusion protein in its membrane environment detect long-lived conformational sub-states}, journal = {Chemphyschem}, volume = {10}, year = {2009}, month = {jul}, pages = {1548{\textendash}1552}, author = {Durrieu, M. P. and Bond, P. J. and Sansom, M. S. and Lavery, R. and Marc Baaden} } @article {2009|1435, title = {{C}omplex molecular assemblies at hand via interactive simulations}, journal = {J. Comput. Chem.}, volume = {30}, year = {2009}, month = {nov}, pages = {2375{\textendash}2387}, author = {Delalande, O. and Nicolas F{\'e}rey and Grasseau, G. and Marc Baaden} } @article {2009|2017, title = {The Conversion of Helix H2 to beta-Sheet Is Accelerated in the Monomer and Dimer of the Prion Protein upon T183A Mutation}, journal = {J. Phys. Chem. B}, volume = {113}, number = {19}, year = {2009}, month = {may}, pages = {6942{\textendash}6948}, doi = {10.1021/jp900334s}, author = {Y Chebaro and Philippe Derreumaux} } @article {2009|1394, title = {Disulfide bond substitution by directed evolution in an engineered binding-protein scaffold.}, journal = {Chembiochem}, volume = {10}, year = {2009}, pages = {1349{\textendash}1359}, author = {Antoine Drevelle and Agathe Urvoas and M{\'e}riam Ben Hamida-Rebai and G{\'e}rard Van Vooren and Magali Nicaise and Marie Valerio-Lepiniec and Michel Desmadril and Charles H. Robert and Philippe Minard} } @article {2009|2018, title = {Energy Flow and Long-Range Correlations in Guanine-Binding Riboswitch: A Nonequilibrium Molecular Dynamics Study}, journal = {J. Phys. Chem. B}, volume = {113}, number = {27}, year = {2009}, month = {jul}, pages = {9340{\textendash}9347}, keywords = {Binding Sites, Computer Simulation, Energy Transfer, Guanine, Ligands, Models, Molecular, Nucleic Acid Conformation, RNA, Temperature}, doi = {10.1021/jp902013s}, author = {Phuong Hoang Nguyen and Philippe Derreumaux and Stock, Gerhard} } @conference {2009, title = {Exploring amyloid aggregates with the OPEP coarse-grained force field}, booktitle = {Abstracts of Papers of the American Chemical Society}, volume = {238}, year = {2009}, author = {Philippe Derreumaux} } @article {2009|1436, title = {A fast method for large-scale De Novo peptide and miniprotein structure prediction.}, journal = {J. Comput. Chem.}, year = {2009}, month = {jun}, doi = {10.1002/jcc.21365}, author = {Julien Maupetit and Philippe Derreumaux and Pierre Tuffery} } @article {2009|1614, title = {Induced beta-Barrel Formation of the Alzheimer{\textquoteright}s A beta 25-35 Oligomers on Carbon Nanotube Surfaces: Implication for Amyloid Fibril Inhibition}, journal = {Biophys. J.}, volume = {97}, number = {6}, year = {2009}, month = {sep}, pages = {1795{\textendash}1803}, doi = {10.1016/j.bpj.2009.07.014}, author = {Fu, Zhaoming and Luo, Yin and Philippe Derreumaux and Wei, Guanghong} } @article {2009|1387, title = {Induced beta-barrel formation of the Alzheimer{\textquoteright}s Abeta25-35 oligomers on carbon nanotube surfaces: implication for amyloid fibril inhibition.}, journal = {Biophys. J.}, volume = {97}, number = {6}, year = {2009}, month = {sep}, pages = {1795{\textendash}1803}, doi = {10.1016/j.bpj.2009.07.014}, author = {Zhaoming Fu and Yin Luo and Philippe Derreumaux and Guanghong Wei} } @article {2009|1438, title = {{A}n optimized extended {D}{N}{A} kappa {B} site that enhances plasmid {D}{N}{A} nuclear import and gene expression}, journal = {J. Gene Med.}, volume = {11}, year = {2009}, month = {may}, pages = {401{\textendash}411}, author = {Goncalves, C. and Ardourel, M. Y. and Decoville, M. and Breuzard, G. and Midoux, P. and Hartmann, B. and Pichon, C.} } @article {2009|1384, title = {New Insight into the interaction between erbin and smad3: a non-classical binding interface for the erbin PDZ domain}, journal = {Biochem. Biophys. Res. Commun.}, volume = {378}, number = {3}, year = {2009}, pages = {360{\textendash}365}, author = {N Deliot and Matthieu Chavent and C Nourry and P Lecine and C Arnaud and A Hermant and B Maigret and J.-P. Borg} } @article {2009|1734, title = {PEP-FOLD: an online resource for de novo peptide structure prediction}, journal = {Nucleic Acids Res.}, volume = {37}, year = {2009}, month = {jul}, pages = {W498-W503}, doi = {10.1093/nar/gkp323}, author = {Maupetit, Julien and Philippe Derreumaux and Pierre Tuffery} } @article {2009|1942, title = {PEP-FOLD: an online resource for de novo peptide structure prediction.}, journal = {Nucleic Acids Res.}, volume = {37}, number = {Web Server issue}, year = {2009}, month = {jul}, pages = {W498{\textendash}W503}, keywords = {Algorithms, Internet, Models, Molecular, Peptides, Protein, Protein Conformation, Reproducibility of Results, Sequence Analysis, Software, User-Computer Interface}, doi = {10.1093/nar/gkp323}, author = {Julien Maupetit and Philippe Derreumaux and Pierre Tuffery} } @article {2009|1830, title = {Replica exchange molecular dynamics simulations of coarse-grained proteins in implicit solvent.}, journal = {J. Phys. Chem. B}, volume = {113}, number = {1}, year = {2009}, month = {jan}, pages = {267{\textendash}274}, keywords = {Amino Acid Sequence, Computer Simulation, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Peptides, Protein Folding, Protein Structure, Proteins, Secondary, Solvents, Temperature, Thermodynamics}, doi = {10.1021/jp805309e}, author = {Y Chebaro and Xiao Dong and Rozita Laghaei and Philippe Derreumaux and Normand Mousseau} } @article {2009|2009, title = {Structural diversity of the soluble trimers of the human amylin(20-29) peptide revealed by molecular dynamics simulations}, journal = {J. Chem. Phys.}, volume = {130}, number = {12}, year = {2009}, month = {mar}, pages = {125101}, keywords = {Amino Acid Sequence, Amyloid, Humans, Models, Molecular, Molecular Sequence Data, Peptide Fragments, Protein Multimerization, Protein Structure, Quaternary, Solubility, Solvents}, doi = {10.1063/1.3097982}, author = {Mo, Yuxiang and Lu, Yan and Wei, Guanghong and Philippe Derreumaux} } @article {2009|1916, title = {Structures and Thermodynamics of Alzheimer{\textquoteright}s Amyloid-beta A beta(16-35) Monomer and Dimer by Replica Exchange Molecular Dynamics Simulations: Implication for Full-Length A beta Fibrillation}, journal = {J. Phys. Chem. B}, volume = {113}, number = {21}, year = {2009}, month = {may}, pages = {7668{\textendash}7675}, doi = {10.1021/jp900425e}, author = {Y Chebaro and Mousseau, Normand and Philippe Derreumaux} } @article {2009|1986, title = {Targeting the early steps of A beta 16-22 protofibril disassembly by N-methylated inhibitors: A numerical study}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {75}, number = {2}, year = {2009}, month = {may}, pages = {442{\textendash}452}, doi = {10.1002/prot.22254}, author = {Y Chebaro and Philippe Derreumaux} } @article {2009|2019, title = {Thermodynamics and dynamics of amyloid peptide oligomerization are sequence dependent}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {75}, number = {4}, year = {2009}, month = {jun}, pages = {954{\textendash}963}, keywords = {Amino Acid Sequence, Amyloid beta-Protein, beta 2-Microglobulin, Cluster Analysis, Computer Simulation, Models, Molecular, Peptide Fragments, Protein Multimerization, Protein Structure, Secondary, Structure-Activity Relationship, Thermodynamics}, doi = {10.1002/prot.22305}, author = {Lu, Yan and Philippe Derreumaux and Guo, Zhi and Mousseau, Normand and Wei, Guanghong} } @article {2009|1504, title = {{X}-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation}, journal = {Nature}, volume = {457}, year = {2009}, month = {jan}, pages = {111{\textendash}114}, author = {Bocquet, N. and Nury, H. and Marc Baaden and Le Poupon, C. and Changeux, J. P. and Delarue, M. and Corringer, P. J.} } @article {2008|1615, title = {The beta-strand-loop-beta-strand conformation is marginally populated in beta(2)-microglobulin (20-41) peptide in solution as revealed by replica exchange molecular dynamics simulations}, journal = {Biophys. J.}, volume = {95}, number = {2}, year = {2008}, month = {jul}, pages = {510{\textendash}517}, doi = {10.1529/biophysj.107.125054}, author = {Liang, Chungwen and Philippe Derreumaux and Mousseau, Normand and Wei, Guanghong} } @article {2008|1583, title = {{C}omparative models of {P}2{X}2 receptor support inter-subunit {A}{T}{P}-binding sites}, journal = {Biochem. Biophys. Res. Commun.}, volume = {375}, number = {3}, year = {2008}, month = {oct}, pages = {405{\textendash}409}, author = {Guerlet, G. and Antoine Taly and Prado de Carvalho, L. and Martz, A. and Jiang, R. and Specht, A. and Le Novere, N. and Grutter, T.} } @article {2008|1585, title = {Comparative models of P2X2 receptor support inter-subunit ATP-binding sites}, journal = {Biochem. Biophys. Res. Commun.}, volume = {375}, number = {3}, year = {2008}, pages = {405{\textendash}409}, publisher = {Academic Press}, author = {Guerlet, Guillaume and Antoine Taly and De Carvalho, Lia Prado and Martz, Adeline and Jiang, Ruotian and Specht, Alexandre and Le Novere, Nicolas and Grutter, Thomas} } @article {2008|1884, title = {The complex folding pathways of protein A suggest a multiple-funnelled energy landscape}, journal = {J. Chem. Phys.}, volume = {128}, number = {4}, year = {2008}, month = {jan}, pages = {045101}, doi = {10.1063/1.2812562}, author = {St-Pierre, Jean-Francois and Mousseau, Normand and Philippe Derreumaux} } @article {2008|1695, title = {Does water condense in hydrophobic cavities? A molecular simulation study of hydration in heterogeneous nanopores}, journal = {J. Phys. Chem. C}, volume = {112}, year = {2008}, pages = {10435{\textendash}10445}, author = {Cailliez, Fabien and Guillaume Stirnemann and Boutin, Anne and Demachy, Isabelle and Fuchs, Alain H.} } @article {2008|1883, title = {Energy landscapes of the monomer and dimer of the Alzheimer{\textquoteright}s peptide A beta(1-28)}, journal = {J. Chem. Phys.}, volume = {128}, number = {12}, year = {2008}, month = {mar}, pages = {125108}, doi = {10.1063/1.2890033}, author = {Dong, Xiao and Chen, Wei and Mousseau, Normand and Philippe Derreumaux} } @article {2008|1811, title = {Exploring energy landscapes of protein folding and aggregation}, journal = {Front. Biosci.}, volume = {13}, year = {2008}, month = {may}, pages = {4495{\textendash}4516}, doi = {10.2741/3019}, author = {Mousseau, Normand and Philippe Derreumaux} } @conference {2008|1544, title = {Free energy surface of Abeta(16-22) complexed by N-methylated Abeta16-22 inhibitors}, booktitle = {Publication Series of the John von Neumann Institute for Computing NIC Series}, volume = {40}, year = {2008}, pages = {177{\textendash}179}, author = {Y Chebaro and Philippe Derreumaux} } @conference {2008|1557, title = {From Interactive to Immersive Molecular Dynamics}, booktitle = {Workshop on Virtual Reality Interaction and Physical Simulation (VRIPHYS 08 - Eurographics)}, year = {2008}, month = {nov}, pages = {89{\textendash}96}, address = {Grenoble - France}, author = {Nicolas F{\'e}rey and O. Delalande and G. Grasseau and Marc Baaden}, editor = {F. Faure and M. Teschner} } @article {2008, title = {Interactions between neuronal fusion proteins explored by molecular dynamics}, journal = {Biophys. J.}, volume = {94}, number = {9}, year = {2008}, month = {may}, pages = {3436{\textendash}3446}, author = {Durrieu, Marie-Pierre and Lavery, Richard and Marc Baaden} } @article {2008|1480, title = {Multiple-step virtual screening using VSM-G: Overview and validation of fast geometrical matching enrichment}, journal = {J. Mol. Model.}, volume = {14}, number = {5}, year = {2008}, pages = {393{\textendash}401}, author = {A Beautrait and V Leroux and Matthieu Chavent and L Ghemtio and M.-D Devignes and M Smail-Tabbone and W Cai and X Shao and G Moreau and P Bladon and J Yao and B Maigret} } @conference {2008|1545, title = {OPERA: An OPtimized coarsed-grained Energy model for RnA}, booktitle = {Publication Series of the John von Neumann Institute for Computing NIC Series}, volume = {40}, year = {2008}, pages = {185{\textendash}187}, author = {C. Colas and Phuong Hoang Nguyen and J-C. Gelly and Philippe Derreumaux} } @article {2008|1804, title = {Role of the region 23-28 in A beta fibril formation: Insights from simulations of the monomers and dimers of Alzheimer{\textquoteright}s peptides A beta 40 and A beta 42}, journal = {Curr. Alzheimer Res.}, volume = {5}, number = {3}, year = {2008}, month = {jun}, pages = {244{\textendash}250}, doi = {10.2174/156720508784533330}, author = {Melquiond, Adrien and Dong, Xiao and Mousseau, Normand and Philippe Derreumaux} } @article {2008|1812, title = {Self-assembly of amyloid-forming peptides by molecular dynamics simulations}, journal = {Front. Biosci.}, volume = {13}, year = {2008}, month = {may}, pages = {5681{\textendash}5692}, author = {Wei, Guanghong and Song, Wei and Philippe Derreumaux and Mousseau, Normand} } @article {2008|1915, title = {Self-assembly of the beta 2-microglobulin NHVTLSQ peptide using a coarse-grained protein model reveals beta-barrel species}, journal = {J. Phys. Chem. B}, volume = {112}, number = {14}, year = {2008}, month = {apr}, pages = {4410{\textendash}4418}, doi = {10.1021/jp710592v}, author = {Song, Wei and Wei, Guanghong and Mousseau, Normand and Philippe Derreumaux} } @conference {2008|1543, title = {Simulating the early steps of amyloid fibril formation and disassembly}, booktitle = {Publication Series of the John von Neumann Institute for Computing NIC Series}, volume = {40}, year = {2008}, pages = {7{\textendash}12}, author = {Philippe Derreumaux} } @conference {2008|1553, title = {A VR Framework for Interacting with Molecular Simulations}, booktitle = {Symposium on Virtual Reality Software and Technology (ACM-VRST 2008)}, year = {2008}, month = {oct}, pages = {91{\textendash}94}, address = {Bordeaux - France}, author = {Nicolas F{\'e}rey and O. Delalande and G. Grasseau and Marc Baaden} } @conference {2007|1517, title = {Atomistic modeling of the membrane-embedded synaptic fusion complex: a grand challenge project on the DEISA HPC infrastructure}, booktitle = {ParCo 2007, Parallel Computing: Architectures, Algorithms and Applications}, volume = {38}, year = {2007}, pages = {729{\textendash}736}, publisher = {John von Neumann Institute for Computing, Juelich, Germany.}, organization = {John von Neumann Institute for Computing, Juelich, Germany.}, url = {http://www.booksonline.iospress.nl/Content/View.aspx?piid=8468}, author = {E. Krieger and L. Leger and M.P. Durrieu and N. Taib and P. Bond and M. Laguerre and R. Lavery and M.S.P. Sansom and Marc Baaden}, editor = {C.B.G.R. Joubert and F. Peters and T. Lippert and M. Buecker and B. Gibbon and and B. Mohr} } @article {2007|1985, title = {A coarse-grained protein force field for folding and structure prediction}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {69}, number = {2}, year = {2007}, month = {nov}, pages = {394{\textendash}408}, doi = {10.1002/prot.21505}, author = {Maupetit, Julien and Pierre Tuffery and Philippe Derreumaux} } @article {2007|1882, title = {Coarse-grained protein molecular dynamics simulations}, journal = {J. Chem. Phys.}, volume = {126}, number = {2}, year = {2007}, month = {jan}, pages = {025101}, doi = {10.1063/1.2408414}, author = {Philippe Derreumaux and Mousseau, Normand} } @article {2007|2013, title = {Computational Simulations of the Early Steps of Protein Aggregation}, journal = {Prion}, volume = {1}, number = {1}, year = {2007}, month = {jan}, pages = {3{\textendash}8}, author = {Wei, Guanghong and Mousseau, Normand and Philippe Derreumaux} } @article {2007|1776, title = {The conserved glycine/alanine residue of the active-site loop containing the putative acetylCoA-binding motif is essential for the overall structural integrity of Mesorhizobium loti arylamine N-acetyltransferase 1}, journal = {Biochem. Biophys. Res. Commun.}, volume = {361}, number = {1}, year = {2007}, month = {sep}, pages = {256{\textendash}262}, doi = {10.1016/j.bbrc.2007.07.034}, author = {Atmane, Noureddine and Dairou, Julien and Flatters, Delphine and Martins, Marta and Pluvinage, Benjamin and Philippe Derreumaux and Dupret, Jean-Marie and Rodrigues-Lima, Fernando} } @inbook {2007|1774, title = {{F}lexible macromolecular docking: {A}n overview of recent progress}, volume = {Recent Research Adv. in Structural BioInformatics}, year = {2007}, pages = {249{\textendash}274}, publisher = {Research Signpost}, organization = {Research Signpost}, chapter = {10}, author = {K. Bastard and Chantal Pr{\'e}vost}, editor = {A. G. De Brevern} } @article {2007|1954, title = {{P}robing amyloid fibril formation of the {N}{F}{G}{A}{I}{L} peptide by computer simulations}, journal = {J. Chem. Phys.}, volume = {126}, number = {6}, year = {2007}, month = {feb}, pages = {065101}, doi = {10.1063/1.2435358}, author = {Melquiond, A. and Gelly, J.C. and Mousseau, N. and Philippe Derreumaux} } @article {2007|1588, title = {Probing the flexibility of the bacterial reaction center: The wild-type protein is more rigid than two site-specific mutants}, journal = {Biochemistry}, volume = {46}, number = {51}, year = {2007}, month = {dec}, pages = {14960{\textendash}14968}, doi = {10.1021/bi7004416}, author = {S Sacquin-Mora and Sebban, P. and Derrien, V. and Frick, B. and Richard Lavery and Alba-Simionesco, C.} } @article {2007|1728, title = {{A} prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family}, journal = {Nature}, volume = {445}, number = {7123}, year = {2007}, month = {jan}, pages = {116{\textendash}119}, author = {Bocquet, N. and Prado de Carvalho, L. and Cartaud, J. and Neyton, J. and Le Poupon, C. and Antoine Taly and Grutter, T. and Jean-Pierre Changeux and Corringer, P. J.} } @inbook {2007|1563, title = {Recent Research Adv. in Structural BioInformatics}, year = {2007}, pages = {249{\textendash}274}, publisher = {Research signpost, Trivandrum, India}, organization = {Research signpost, Trivandrum, India}, chapter = {Flexible macromolecular docking: An overview of recent progress}, author = {K. Bastard and Chantal Pr{\'e}vost}, editor = {A.G. de Brevern} } @article {2007|1881, title = {Sampling small-scale and large-scale conformational changes in proteins and molecular complexes}, journal = {J. Chem. Phys.}, volume = {126}, number = {10}, year = {2007}, month = {mar}, pages = {105101}, doi = {10.1063/1.2710270}, author = {Yun, Mi-Ran and Mousseau, N. and Philippe Derreumaux} } @article {2007|1616, title = {Structural and hydration properties of the partially unfolded states of the prion protein}, journal = {Biophys. J.}, volume = {93}, number = {4}, year = {2007}, month = {aug}, pages = {1284{\textendash}1292}, doi = {10.1529/biophysj.107.108613}, author = {De Simone, Alfonso and Zagari, Adriana and Philippe Derreumaux} } @article {2007|1617, title = {Structure and aggregation mechanism of beta 2-microglobulin (83-99) peptides studied by molecular dynamics Simulations}, journal = {Biophys. J.}, volume = {93}, number = {10}, year = {2007}, month = {nov}, pages = {3353{\textendash}3362}, doi = {10.1529/biophysj.107.105585}, author = {Liang, Chungwen and Philippe Derreumaux and Wei, Guanghong} } @inbook {2007|1564, title = {There{\textquoteright}s plenty of room in the middle: multi-scale modelling of biological systems}, year = {2007}, pages = {173{\textendash}195}, publisher = {Research signpost, India}, organization = {Research signpost, India}, chapter = {Recent Advances in Protein engineering}, address = {Trivandrum, Kerala, India}, author = {Marc Baaden and R. Lavery}, editor = {A.G. de Brevern} } @article {2006|1981, title = {Aggregating the amyloid A beta(11-25) peptide into a four-stranded beta-sheet structure}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {65}, number = {4}, year = {2006}, month = {dec}, pages = {877{\textendash}888}, doi = {10.1002/prot.21134}, author = {Boucher, Genevive and Mousseau, Normand and Philippe Derreumaux} } @article {2006|1983, title = {ARTIST: An activated method in internal coordinate space for sampling protein energy landscapes}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {63}, number = {4}, year = {2006}, month = {jun}, pages = {967{\textendash}975}, doi = {10.1002/prot.20938}, author = {Yun, MR and Lavery, R and Mousseau, N and Zakrzewska, K and Philippe Derreumaux} } @article {2006|1880, title = {The conformations of the amyloid-beta (21-30) fragment can be described by three families in solution}, journal = {J. Chem. Phys.}, volume = {125}, number = {8}, year = {2006}, month = {aug}, pages = {084911}, doi = {10.1063/1.2337628}, author = {Chen, Wei and Mousseau, Normand and Philippe Derreumaux} } @article {2006|1943, title = {Hfq variant with altered RNA binding functions}, journal = {Nucleic Acids Res.}, volume = {34}, number = {2}, year = {2006}, pages = {709{\textendash}720}, doi = {10.1093/nar/gkj464}, author = {Ziolkowska, K and Philippe Derreumaux and Folichon, M and Pellegrini, O and Regnier, P and Boni, IV and Hajnsdorf, E} } @article {2006|2008, title = {{I}dentification of two critical residues within the {C}ys-loop sequence that determine fast-gating kinetics in a pentameric ligand-gated ion channel}, journal = {J. Mol. Neurosci.}, volume = {30}, number = {1-2}, year = {2006}, pages = {63{\textendash}64}, publisher = {Springer}, author = {Grutter, T. and de Carvalho, L. P. and Dufresne, V. and Antoine Taly and Jean-Pierre Changeux} } @article {2006|1754, title = {{I}mplications of the quaternary twist allosteric model for the physiology and pathology of nicotinic acetylcholine receptors}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {103}, number = {45}, year = {2006}, month = {nov}, pages = {16965{\textendash}16970}, author = {Antoine Taly and Corringer, P. J. and Grutter, T. and Prado de Carvalho, L. and Karplus, M. and Jean-Pierre Changeux} } @article {2006|1618, title = {Impact of the mutation A21G (Flemish variant) on Alzheimer{\textquoteright}s beta-amyloid dimers by molecular dynamics simulations}, journal = {Biophys. J.}, volume = {91}, number = {10}, year = {2006}, month = {nov}, pages = {3829{\textendash}3840}, doi = {10.1526/biophysj.106.090993}, author = {Huet, Alexis and Philippe Derreumaux} } @article {2006|1757, title = {Implications of the quaternary twist allosteric model for the physiology and pathology of nicotinic acetylcholine receptors}, journal = {Proceedings of the National Academy of Sciences}, volume = {103}, number = {45}, year = {2006}, pages = {16965{\textendash}16970}, publisher = {National Acad Sciences}, author = {Antoine Taly and Corringer, Pierre-Jean and Grutter, Thomas and De Carvalho, Lia Prado and Karplus, Martin and Jean-Pierre Changeux} } @article {2006|1810, title = {Normal mode analysis as a prerequisite for drug design: Application to matrix metalloproteinases inhibitors}, journal = {Febs Lett.}, volume = {580}, number = {22}, year = {2006}, month = {oct}, pages = {5130{\textendash}5136}, abstract = {We demonstrate the utility of normal mode analysis in correctly predicting the binding modes of inhibitors in the active sites of matrix metalloproteinases (MMPs). We show the accuracy in predicting the positions of MMP-3 inhibitors is strongly dependent on which structure is used as the target, especially when it has been energy minimized. This dependency can be overcome by using intermediate structures generated along one of the normal modes previously calculated for a given target. These results may be of prime importance for further in silico drug discovery.}, doi = {10.1016/j.febslet.2006.08.037}, author = {Nicolas Floquet and Jean-Didier Mar{\'e}chal and Marie-Ange Badet-Denisot and Charles H Robert and Manuel Dauchez and David Perahia} } @article {2006|1658, title = {Odorant Binding and Conformational Dynamics in the Odorant-binding Protein}, journal = {J. Biol. Chem.}, volume = {281}, number = {40}, year = {2006}, month = {oct}, pages = {29929{\textendash}29937}, abstract = {In mammals, the olfactory epithelium secretes odorant-binding proteins (OBPs), which are lipocalins found freely dissolved in the mucus layer protecting the olfactory neurons. OBPs may act as passive transporters of predominantly hydrophobic odorant molecules across the aqueous mucus layer, or they may play a more active role in which the olfactory neuronal receptor recognizes the OBP-ligand complex. To better understand the molecular events accompanying the initial steps in the olfaction process, we have performed molecular dynamics studies of rat and pig OBPs with the odorant molecule thymol. These calculations provide an atomic level description of conformational changes and pathway intermediates that remain difficult to study directly. A series of eight independent molecular dynamics trajectories of rat OBP permitted the observation of a consensus pathway for ligand unbinding and the calculation of the potential of mean force (PMF) along this path. Titration microcalorimetry confirmed the specific binding of thymol to this protein with a strong hydrophobic component. In both rat and pig OBPs we observed lipocalin strand pair opening in the presence of ligand, consistent with potential roles of these proteins in olfactive receptor recognition.}, doi = {10.1074/jbc.M604869200}, author = {Eric Hajjar and David Perahia and Helene D{\'e}bat and Claude Nespoulous and Charles H. Robert} } @conference {2006, title = {PHYS 4-Applications of activated methods to proteins and materials science}, booktitle = {Abstracts of Papers of the American Chemical Society}, volume = {232}, year = {2006}, author = {Mousseau, Normand and Barkema, Gerard T. and Chubynsky, Mykyta V. and Philippe Derreumaux and El-Mellouhi, Fedwa and Vocks, Henk} } @article {2006|1514, title = {Protein Peeling 2: a web server to convert protein structures into series of protein units}, journal = {Nucleic Acids Res.}, volume = {34}, number = {Sp. Iss. SI}, year = {2006}, month = {jul}, pages = {W75-W78}, author = {Gelly, J. -C. and Etchebest, C. and Hazout, S. and de Brevern, A. G.} } @article {2006|1386, title = {{\textquoteleft}Protein Peeling{\textquoteright}: an approach for splitting a 3D protein structure into compact fragments}, journal = {Bioinformatics}, volume = {22}, number = {2}, year = {2006}, pages = {129{\textendash}133}, author = {Gelly, JC and de Brevern, AG and Hazout, S} } @article {2006|1842, title = {Structural changes of region 1-16 of the Alzheimer disease amyloid beta-peptide upon zinc binding and in vitro aging}, journal = {J. Biol. Chem.}, volume = {281}, number = {4}, year = {2006}, pages = {2151{\textendash}2161}, author = {Severine Zirah and Sergey A. Kozin and Alexey K Mazur and Alain Blond and Michel Cheminant and Isabelle Segalas-Milazzo and Pascale Debey and Sylvie Rebuffat} } @article {2006|1982, title = {Structures of soluble amyloid oligomers from computer simulations}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {65}, number = {1}, year = {2006}, month = {oct}, pages = {180{\textendash}191}, doi = {10.1002/prot.21100}, author = {Melquiond, Adrien and Mousseau, Normand and Philippe Derreumaux} } @article {2005|1980, title = {The beta alpha beta alpha beta alpha elementary Supersecondary structure of the Rossmann fold from porcine lactate dehydrogenase exhibits characteristics of a molten globule}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {60}, number = {4}, year = {2005}, month = {sep}, pages = {740{\textendash}745}, doi = {10.1002/prot.20507}, author = {Coincon, M and Heitz, A and Chiche, L and Philippe Derreumaux} } @article {2005|1631, title = {{A} chimera encoding the fusion of an acetylcholine-binding protein to an ion channel is stabilized in a state close to the desensitized form of ligand-gated ion channels}, journal = {C. R. Biol.}, volume = {328}, number = {3}, year = {2005}, month = {mar}, pages = {223{\textendash}234}, author = {Grutter, T. and Prado de Carvalho, L. and Virginie, D. and Antoine Taly and Fischer, M. and Jean-Pierre Changeux} } @article {2005|1979, title = {Dependency between consecutive local conformations helps assemble protein structures from secondary structures using Go potential and greedy algorithm}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {61}, number = {4}, year = {2005}, month = {dec}, pages = {732{\textendash}740}, doi = {10.1002/prot.20698}, author = {Pierre Tuffery and Philippe Derreumaux} } @article {2005|1378, title = {Exploring the early steps of amyloid peptide aggregation by computers}, journal = {Acc. Chem. Res.}, volume = {38}, number = {11}, year = {2005}, pages = {885{\textendash}891}, author = {Mousseau, N and Philippe Derreumaux} } @conference {2005, title = {Following the aggregation of amyloid-forming peptides by computer simulations.}, booktitle = {Abstracts of Papers of the American Chemical Society}, volume = {229}, number = {Part 2}, year = {2005}, pages = {U735}, author = {Philippe Derreumaux} } @article {2005|1879, title = {Following the aggregation of amyloid-forming peptides by computer simulations}, journal = {J. Chem. Phys.}, volume = {122}, number = {17}, year = {2005}, month = {may}, pages = {174904}, doi = {10.1063/1.1886725}, author = {Melquiond, A and Boucher, G and Mousseau, N and Philippe Derreumaux} } @article {2005|1400, title = {Hydration and thermodynamic equilibrium of non-ionic surfactant in solution}, journal = {Coll Surf A}, volume = {261}, year = {2005}, pages = {93{\textendash}99}, author = {Briganti, Giuseppe and D{\textquoteright}arrigo, Giovanni and Maccarini, Marco and Pierleoni, Carlo and Sterpone, Fabio} } @article {2005|1900, title = {Improved greedy algorithm for protein structure reconstruction}, journal = {J. Comput. Chem.}, volume = {26}, number = {5}, year = {2005}, month = {apr}, pages = {506{\textendash}513}, doi = {10.1002/jcc.20181}, author = {Pierre Tuffery and Guyon, F and Philippe Derreumaux} } @article {2005|2011, title = {{M}olecular tuning of fast gating in pentameric ligand-gated ion channels}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {102}, number = {50}, year = {2005}, month = {dec}, pages = {18207{\textendash}18212}, publisher = {National Acad Sciences}, author = {Grutter, T. and de Carvalho, L. P. and Dufresne, V. and Antoine Taly and Edelstein, S. J. and Jean-Pierre Changeux} } @article {2005|2003, title = {{N}ormal mode analysis suggests a quaternary twist model for the nicotinic receptor gating mechanism}, journal = {Biophys. J.}, volume = {88}, number = {6}, year = {2005}, month = {jun}, pages = {3954{\textendash}3965}, publisher = {Cell Press}, author = {Antoine Taly and Delarue, M. and Grutter, T. and Nilges, M. and Le Novere, N. and Corringer, P. J. and Jean-Pierre Changeux} } @article {2005|1952, title = {Navigation and analysis of the energy landscape of small proteins using the activation-relaxation technique}, journal = {Phys. Biol.}, volume = {2}, number = {4, Sp. Iss. SI}, year = {2005}, month = {dec}, pages = {S101-S107}, doi = {10.1088/1478-3975/2/4/S04}, author = {Mousseau, N and Philippe Derreumaux and Gilbert, G} } @article {2004|1867, title = {The antitumor properties of the alpha 3(IV)-(185-203) peptide from the NC1 domain of type IV collagen (tumstatin) are conformation-dependent}, journal = {J. Biol. Chem.}, volume = {279}, number = {3}, year = {2004}, month = {jan}, pages = {2091{\textendash}2100}, doi = {10.1074/jbc.M307736200}, author = {Floquet, N and Pasco, S and Ramont, L and Philippe Derreumaux and Laronze, JY and Nuzillard, JM and Maquart, FX and Alix, AJP and Monboisse, JC} } @article {2004|1978, title = {Complex folding pathways in a simple beta-hairpin}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {56}, number = {3}, year = {2004}, month = {aug}, pages = {464{\textendash}474}, doi = {10.1002/prot.20127}, author = {Wei, GH and Mousseau, N and Philippe Derreumaux} } @article {2004|1537, title = {Conformational sampling and dynamics of membrane proteins from 10-nanosecond computer simulations}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {57}, number = {4}, year = {2004}, month = {dec}, pages = {783{\textendash}791}, author = {Faraldo-Gomez, JD and Forrest, LR and Marc Baaden and Bond, PJ and Domene, C and Patargias, G and Cuthbertson, J and Sansom, MSP} } @article {2004|1647, title = {Critical role of the C-terminal segment in the maturation and export to the cell surface of the homopentameric $\alpha$7{\textendash}5HT3A receptor}, journal = {Eur. J. Neurosci.}, volume = {20}, number = {8}, year = {2004}, pages = {2022{\textendash}2030}, publisher = {Wiley Online Library}, author = {Pons, S and Sallette, J and Bourgeois, JP and Antoine Taly and Jean-Pierre Changeux and Devillers-Thi{\'e}ry, A} } @article {2004|1807, title = {The C-terminal domain of Escherichia coli Hfq increases the stability of the hexamer}, journal = {Eur. J. Biochem.}, volume = {271}, number = {7}, year = {2004}, month = {apr}, pages = {1258{\textendash}1265}, doi = {10.1111/j.1432-1033.2004.04026.x}, author = {Arluison, V and Folichon, M and Marco, S and Philippe Derreumaux and Pellegrini, O and Seguin, J and Hajnsdorf, E and Regnier, P} } @article {2004|1939, title = {Early steps of amyloid-petide oligomerisation explored by simulations}, journal = {Neurobiol. Aging}, volume = {25}, number = {Suppl. 2}, year = {2004}, month = {jul}, pages = {S143}, doi = {10.1016/S0197-4580(04)80481-0}, author = {Philippe Derreumaux and Wei, GH and Santini, S and Mousseau, NN} } @article {2004|1928, title = {Exploring the early steps of aggregation of amyloid-forming peptide KFFE}, journal = {Journal of Physics-condensed Matter}, volume = {16}, number = {44, Sp. Iss. SI}, year = {2004}, month = {nov}, pages = {S5047-S5054}, doi = {10.1088/0953-8984/16/44/002}, author = {Wei, GH and Mousseau, N and Philippe Derreumaux} } @article {2004|1791, title = {Helix H1 of the prion protein is rather stable against environmental perturbations: molecular dynamics of mutation and deletion variants of PrP(90-231)}, journal = {Cell. Mol. Life Sci.}, volume = {61}, number = {7-8}, year = {2004}, month = {apr}, pages = {951{\textendash}960}, doi = {10.1007/s00018-003-3455-3}, author = {Santini, S and Philippe Derreumaux} } @article {2004|1930, title = {In silico assembly of Alzheimer{\textquoteright}s A beta(16-22) peptide into beta-sheets}, journal = {J. Am. Chem. Soc.}, volume = {126}, number = {37}, year = {2004}, month = {sep}, pages = {11509{\textendash}11516}, doi = {10.1021/ja047286i}, author = {Santini, S and Mousseau, N and Philippe Derreumaux} } @article {2004|1994, title = {Pathway complexity of Alzheimer{\textquoteright}s beta-amyloid A beta(16-22) peptide assembly}, journal = {Structure}, volume = {12}, number = {7}, year = {2004}, month = {jul}, pages = {1245{\textendash}1255}, doi = {10.1016/j.str.2004.04.018}, author = {Santini, S and Wei, GH and Mousseau, N and Philippe Derreumaux} } @article {2004|1620, title = {Sampling the self-assembly pathways of KFFE hexamers}, journal = {Biophys. J.}, volume = {87}, number = {6}, year = {2004}, month = {dec}, pages = {3648{\textendash}3656}, doi = {10.1529/biophysj.104.047688}, author = {Wei, G. H. and Mousseau, N. and Philippe Derreumaux} } @article {2004|1787, title = {Structural characterization of VGVAPG, an elastin-derived peptide}, journal = {Biopolymers}, volume = {76}, number = {3}, year = {2004}, pages = {266{\textendash}280}, doi = {10.1002/bip.20029}, author = {Floquet, N and Hery-Huynh, S and Dauchez, M and Philippe Derreumaux and Tamburro, AM and Alix, AJP} } @article {2003|1428, title = {Exploring the folding pathways of proteins through energy landscape sampling: Application to Alzheimer{\textquoteright}s beta-amyloid peptide}, journal = {Internet Electron. J. Mol. Des.}, volume = {2}, year = {2003}, pages = {564{\textendash}577}, author = {S. Santini and G. Wei and N. Mousseau and Philippe Derreumaux} } @article {2003|1914, title = {Generating conformations for two zinc-binding sites of HIV-1 nucleocapsid protein from random conformations by a hierarchical procedure and polarizable force field}, journal = {J. Phys. Chem. B}, volume = {107}, number = {20}, year = {2003}, month = {may}, pages = {4862{\textendash}4870}, doi = {10.1021/jp022527z}, author = {Gresh, N and Philippe Derreumaux} } @article {2003|1990, title = {Impact of the tail and mutations G131V and M129V on prion protein flexibility}, journal = {Proteins-structure Function and Genetics}, volume = {51}, number = {2}, year = {2003}, month = {may}, pages = {258{\textendash}265}, doi = {10.1002/prot.10348}, author = {Santini, S and Claude, JB and Audic, S and Philippe Derreumaux} } @article {2003|1877, title = {Role of supersecondary structural elements in protein G folding}, journal = {J. Chem. Phys.}, volume = {119}, number = {9}, year = {2003}, month = {sep}, pages = {4940{\textendash}4944}, doi = {10.1063/1.1596891}, author = {Philippe Derreumaux} } @article {2003|1876, title = {Sampling the complex energy landscape of a simple beta-hairpin}, journal = {J. Chem. Phys.}, volume = {119}, number = {13}, year = {2003}, month = {oct}, pages = {6403{\textendash}6406}, doi = {10.1063/1.1613642}, author = {Wei, GH and Philippe Derreumaux and Mousseau, N} } @article {2002|1874, title = {Exploring the energy landscape of proteins: A characterization of the activation-relaxation technique}, journal = {J. Chem. Phys.}, volume = {117}, number = {24}, year = {2002}, month = {dec}, pages = {11379{\textendash}11387}, doi = {10.1063/1.1522373}, author = {Wei, GH and Mousseau, N and Philippe Derreumaux} } @article {2002|1875, title = {Insight into protein topology from Monte Carlo simulations}, journal = {J. Chem. Phys.}, volume = {117}, number = {7}, year = {2002}, month = {aug}, pages = {3499{\textendash}3503}, doi = {10.1063/1.1494427}, author = {Philippe Derreumaux} } @article {2002|1902, title = {Structural modelling of the Sm-like protein Hfq from Escherichia coli}, journal = {J. Mol. Biol.}, volume = {320}, number = {4}, year = {2002}, month = {jul}, pages = {705{\textendash}712}, doi = {10.1016/S0022-2836(02)00548-X}, author = {Arluison, V and Philippe Derreumaux and Allemand, F and Folichon, M and Hajnsdorf, E and Regnier, P} } @article {2001|1989, title = {Computer simulations aimed at structure prediction of supersecondary motifs in proteins}, journal = {Proteins-structure Function and Genetics}, volume = {45}, number = {2}, year = {2001}, month = {nov}, pages = {159{\textendash}166}, doi = {10.1002/prot.1135}, author = {Forcellino, F and Philippe Derreumaux} } @article {2001|1623, title = {Evidence that the 127-164 region of prion proteins has two equi-energetic conformations with beta or alpha features}, journal = {Biophys. J.}, volume = {81}, number = {3}, year = {2001}, month = {sep}, pages = {1657{\textendash}1665}, author = {Philippe Derreumaux} } @article {2001|1903, title = {Sampling activated mechanisms in proteins with the activation-relaxation technique}, journal = {Journal of Molecular Graphics \& Modelling}, volume = {19}, number = {1}, year = {2001}, pages = {78{\textendash}86}, doi = {10.1016/S1093-3263(00)00134-0}, author = {Mousseau, N and Philippe Derreumaux and Barkema, GT and Malek, R} } @article {2001|1841, title = {Sheep prion protein synthetic peptide spanning helix 1 and beta-strand 2 (residues 142-166) shows beta-hairpin structure in solution}, journal = {J. Biol. Chem.}, volume = {276}, number = {49}, year = {2001}, pages = {46364{\textendash}46370}, author = {S. A. Kozin and G. Bertho and Alexey K Mazur and H. Rabesona and J. P. Girault and T. Haertle and M. Takahashi and P. Debey and G. H. Hoa} } @article {2000|1997, title = {Ab initio polypeptide structure prediction}, journal = {Theor. Chem. Acc.}, volume = {104}, number = {1}, year = {2000}, month = {may}, pages = {1{\textendash}6}, doi = {10.1007/s002149900095}, author = {Philippe Derreumaux} } @article {2000, title = {Calix{[}4]arenes as selective extracting agents. An NMR dynamic and conformational investigation of the lanthanide(III) and thorium(IV) complexes}, journal = {Inorg. Chem.}, volume = {39}, number = {10}, year = {2000}, month = {may}, pages = {2033{\textendash}2041}, author = {Lambert, B and Jacques, V and Shivanyuk, A and Matthews, SE and Tunayar, A and Marc Baaden and Wipff, G and Bohmer, V and Desreux, JF} } @article {2000|1958, title = {Generating ensemble averages for small proteins from extended conformations by Monte Carlo simulations}, journal = {Phys. Rev. Lett.}, volume = {85}, number = {1}, year = {2000}, month = {jul}, pages = {206{\textendash}209}, doi = {10.1103/PhysRevLett.85.206}, author = {Philippe Derreumaux} } @article {2000|1899, title = {Predicting helical hairpins from sequences by Monte Carlo simulations}, journal = {J. Comput. Chem.}, volume = {21}, number = {7}, year = {2000}, month = {may}, pages = {582{\textendash}589}, doi = {10.1002/(SICI)1096-987X(200005)21:7<582}, author = {Philippe Derreumaux} } @conference {2000|1532, title = {Separation of radioactive cations by liquid-liquid extraction: computer simulations of water / oil solutions of salts and ionophores}, booktitle = {Proceedings of the Euradwaste 1999 conference}, year = {2000}, pages = {390{\textendash}393}, address = {EC, Luxembourg}, author = {Marc Baaden and F. Berny and N. Muzet and R. Schurhammer and G. Wipff}, editor = {C. Davies} } @article {1999|1803, title = {Ab initio prediction of polypeptide structure from its sequence}, journal = {Comput. Phys. Commun.}, volume = {122}, number = {Sp. Iss. SI}, year = {1999}, month = {sep}, pages = {139{\textendash}140}, doi = {10.1016/S0010-4655(99)00299-4}, author = {Philippe Derreumaux} } @article {1999|1873, title = {From polypeptide sequences to structures using Monte Carlo simulations and an optimized potential}, journal = {J. Chem. Phys.}, volume = {111}, number = {5}, year = {1999}, month = {aug}, pages = {2301{\textendash}2310}, doi = {10.1063/1.479501}, author = {Philippe Derreumaux} } @article {1998|1454, title = {{D}{N}{A} crossovers and type {I}{I} {D}{N}{A} topoisomerases: {A} thermodynamical study}, journal = {J. Mol. Biol.}, volume = {284}, year = {1998}, month = {dec}, pages = {1279{\textendash}1287}, author = {Sikorav, J.L. and Duplantier, B. and Jannink, G. and Y Timsit} } @article {1998|1872, title = {Finding the low-energy forms of avian pancreatic polypeptide with the diffusion-process-controlled Monte Carlo method}, journal = {J. Chem. Phys.}, volume = {109}, number = {4}, year = {1998}, month = {jul}, pages = {1567{\textendash}1574}, doi = {10.1063/1.476708}, author = {Philippe Derreumaux} } @article {1998|1624, title = {The loop opening/closing motion of the enzyme triosephosphate isomerase}, journal = {Biophys. J.}, volume = {74}, number = {1}, year = {1998}, month = {jan}, pages = {72{\textendash}81}, author = {Philippe Derreumaux and Schlick, T.} } @article {1998|1453, title = {{S}ymmetry and chirality in topoisomerase {I}{I}-{D}{N}{A} crossover recognition}, journal = {J. Mol. Biol.}, volume = {284}, year = {1998}, month = {dec}, pages = {1289{\textendash}1299}, author = {Y Timsit and Duplantier, B. and Jannink, G. and Sikorav, J.L.} } @article {1997|1871, title = {A diffusion process-controlled Monte Carlo method for finding the global energy minimum of a polypeptide chain .1. Formulation and test on a hexadecapeptide}, journal = {J. Chem. Phys.}, volume = {106}, number = {12}, year = {1997}, month = {mar}, pages = {5260{\textendash}5270}, doi = {10.1063/1.473525}, author = {Philippe Derreumaux} } @article {1997|1870, title = {Folding a 20 amino acid alpha beta peptide with the diffusion process-controlled Monte Carlo method}, journal = {J. Chem. Phys.}, volume = {107}, number = {6}, year = {1997}, month = {aug}, pages = {1941{\textendash}1947}, doi = {10.1063/1.474546}, author = {Philippe Derreumaux} } @article {1996|1660, title = {Molecular modelling study of the netropsin complexation with a nucleic acid triple helix}, journal = {J. Biomol. Struct. Dyn.}, volume = {14}, year = {1996}, month = {dec}, pages = {293{\textendash}302}, abstract = {

A detailed molecular mechanical study has been made on the complexes of netropsin with the double stranded oligonucleotide (dA)12.(dT)12 and with the triple helix (dA)12.(dT)12.(dT)12. The complexes were built using computer graphics and energy refined using JUMNA program. In agreement with circular dichroism experiments we have shown that 3 netropsins can bind the minor grooves of the triple helix and of the double helix. The groove geometry in the duplex and in the triplex is very similar. However a detailed analysis of the energetic terms shows, in agreement with thermal denaturation studies, that the affinity of netropsin toward the double helices is larger than towards triple helices.

}, doi = {10.1080/07391102.1996.10508125}, author = {Vovelle, F and Chantal Pr{\'e}vost and Durand, M and Maurizot, J C} } @article {1995|1988, title = {LONG TIMESTEP DYNAMICS OF PEPTIDES BY THE DYNAMICS DRIVER APPROACH}, journal = {Proteins-structure Function and Genetics}, volume = {21}, number = {4}, year = {1995}, month = {apr}, pages = {282{\textendash}302}, doi = {10.1002/prot.340210403}, author = {Philippe Derreumaux and SCHLICK, T} } @article {1995|1869, title = {A NEW SPECTROSCOPIC MOLECULAR MECHANICS FORCE-FIELD - PARAMETERS FOR PROTEINS}, journal = {J. Chem. Phys.}, volume = {102}, number = {21}, year = {1995}, month = {jun}, pages = {8586{\textendash}8605}, doi = {10.1063/1.468848}, author = {Philippe Derreumaux and VERGOTEN, G} } @article {1995|1898, title = {A VIBRATIONAL MOLECULAR-FORCE FIELD OF MODEL COMPOUNDS WITH BIOLOGICAL INTEREST .4. PARAMETERS FOR THE DIFFERENT GLYCOSIDIC LINKAGES OF OLIGOSACCHARIDES}, journal = {J. Comput. Chem.}, volume = {16}, number = {2}, year = {1995}, month = {feb}, pages = {188{\textendash}199}, doi = {10.1002/jcc.540160206}, author = {Dauchez, M and Philippe Derreumaux and LAGANT, P and VERGOTEN, G} } @article {1994|1993, title = {FORCE-FIELD AND VIBRATIONAL-SPECTRA OF OLIGOSACCHARIDES WITH DIFFERENT GLYCOSIDIC LINKAGES .2. MALTOSE MONOHYDRATE, CELLOBIOSE AND GENTIOBIOSE}, journal = {Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy}, volume = {50}, number = {1}, year = {1994}, month = {jan}, pages = {105{\textendash}118}, doi = {10.1016/0584-8539(94)80118-5}, author = {Dauchez, M and LAGANT, P and Philippe Derreumaux and VERGOTEN, G and SEKKAL, M and SOMBRET, B} } @article {1994|1992, title = {FORCE-FIELD AND VIBRATIONAL-SPECTRA OF OLIGOSACCHARIDES WITH DIFFERENT GLYCOSIDIC LINKAGES .1. TREHALOSE DIHYDRATE, SOPHOROSE MONOHYDRATE AND LAMINARIBIOSE}, journal = {Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy}, volume = {50}, number = {1}, year = {1994}, month = {jan}, pages = {87{\textendash}104}, doi = {10.1016/0584-8539(94)80117-7}, author = {Dauchez, M and Philippe Derreumaux and LAGANT, P and VERGOTEN, G and SEKKAL, M and LEGRAND, P} } @article {1994|1897, title = {A TRUNCATED NEWTON MINIMIZER ADAPTED FOR CHARMM AND BIOMOLECULAR APPLICATIONS}, journal = {J. Comput. Chem.}, volume = {15}, number = {5}, year = {1994}, month = {may}, pages = {532{\textendash}552}, doi = {10.1002/jcc.540150506}, author = {Philippe Derreumaux and ZHANG, GH and SCHLICK, T and BROOKS, B} } @article {1994|1909, title = {THE USE OF THE SPASIBA SPECTROSCOPIC POTENTIAL FOR REPRODUCING THE STRUCTURES AND VIBRATIONAL FREQUENCIES OF A SERIES OF ACIDS - ACETIC-ACID, PIVALIC ACID, SUCCINIC ACID, ADIPIC ACID AND L-GLUTAMIC ACID}, journal = {J. Mol. Struct.}, volume = {317}, number = {1-2}, year = {1994}, month = {jan}, pages = {171{\textendash}184}, doi = {10.1016/0022-2860(93)07860-Y}, author = {CHHIBA, M and Philippe Derreumaux and VERGOTEN, G} } @article {1993|1907, title = {COMPARISON OF THE IR AND RAMAN VIBRATIONAL FREQUENCIES AND INTENSITIES OF ALKANES USING THE AMBER AND SPASIBA FORCE-FIELDS - APPLICATION TO ETHANE, AND GAUCHE-N-BUTANE AND TRANS-N-BUTANE}, journal = {J. Mol. Struct.}, volume = {295}, year = {1993}, month = {may}, pages = {223{\textendash}232}, doi = {10.1016/0022-2860(93)85022-M}, author = {Philippe Derreumaux and LAGANT, P and VERGOTEN, G} } @article {1993|1908, title = {HARMONIC AND MOLECULAR-DYNAMICS OF N-OCTANE - COMPARISON BETWEEN THE AMBER AND SPASIBA FORCE-FIELDS}, journal = {J. Mol. Struct.}, volume = {295}, year = {1993}, month = {may}, pages = {233{\textendash}244}, doi = {10.1016/0022-2860(93)85023-N}, author = {Philippe Derreumaux and VERGOTEN, G} } @article {1993|1996, title = {INFLUENCE OF THE SPECTROSCOPIC POTENTIAL-ENERGY FUNCTION SPASIBA ON MOLECULAR-DYNAMICS OF PROTEINS - COMPARISON WITH THE AMBER POTENTIAL}, journal = {Theochem-journal of Molecular Structure}, volume = {105}, year = {1993}, month = {oct}, pages = {55{\textendash}64}, author = {Philippe Derreumaux and VERGOTEN, G} } @article {1993|1673, title = {Investigation of conformational equilibrium of polypeptides by internal coordinate stochastic dynamics: Met-enkephalin}, journal = {J. Biomol. Struct. Dyn.}, volume = {10}, year = {1993}, pages = {143{\textendash}167}, author = {Vladimir E. Dorofeyev and Alexey K Mazur} } @article {1993|1682, title = {Optimization of numerical algorithms for internal coordinate molecular dynamics}, journal = {J. Comput. Phys.}, volume = {107}, year = {1993}, pages = {359{\textendash}366}, author = {Vladimir E. Dorofeyev and Alexey K Mazur} } @article {1993|1906, title = {THE STRUCTURES AND VIBRATIONAL FREQUENCIES OF A SERIES OF ALKANES USING THE SPASIBA FORCE-FIELD}, journal = {J. Mol. Struct.}, volume = {295}, year = {1993}, month = {may}, pages = {203{\textendash}221}, doi = {10.1016/0022-2860(93)85021-L}, author = {Philippe Derreumaux and Dauchez, M and VERGOTEN, G} } @article {1993|1896, title = {VIBRATIONAL MOLECULAR-FORCE FIELD OF MODEL COMPOUNDS WITH BIOLOGIC INTEREST .2. HARMONIC DYNAMICS OF BOTH ANOMERS OF GLUCOSE IN THE CRYSTALLINE STATE}, journal = {J. Comput. Chem.}, volume = {14}, number = {3}, year = {1993}, month = {mar}, pages = {263{\textendash}277}, doi = {10.1002/jcc.540140303}, author = {Dauchez, M and Philippe Derreumaux and VERGOTEN, G} } @article {1992|1626, title = {Global optimization of conformation energy of polypeptides by tunnel algorithm}, journal = {Biophysics}, volume = {37}, year = {1992}, pages = {226{\textendash}230}, author = {M. G. Petuhov and V. E. Dorofeyev and R. A. Abagyan and Alexey K Mazur} } @article {1991|1683, title = {Derivation and testing of explicit equations of motion for polymers described by internal coordinates}, journal = {J. Comput. Phys.}, volume = {92}, year = {1991}, pages = {261{\textendash}272}, author = {Alexey K Mazur and Vladimir E. Dorofeyev and Ruben A. Abagyan} } @article {1991|1987, title = {EFFECT OF UREY-BRADLEY-SHIMANOUCHI FORCE-FIELD ON THE HARMONIC DYNAMICS OF PROTEINS}, journal = {Proteins-structure Function and Genetics}, volume = {11}, number = {2}, year = {1991}, pages = {120{\textendash}132}, doi = {10.1002/prot.340110205}, author = {Philippe Derreumaux and VERGOTEN, G} } @conference {1991|1580, title = {Methodological considerations on molecular dynamics simulations of DNA oligonucleotides}, booktitle = {AIP Conference Proceedings}, year = {1991}, month = {oct}, publisher = {AIP}, organization = {AIP}, abstract = {

Methodological aspects of solvent effects, simulation protocol, analysis and visualization of results, accuracy, and sensitivity of results to force field parametrization are discussed for molecular dynamics simulation on oligonucleotides. Recent results comparing AMBER, CHARMM and GROMOS force fields are included. The calculation of build\‚{\"A}{\^e}up curves for the nuclear Overhauser effect from simulations is also described.

}, doi = {10.1063/1.41314}, author = {Beveridge, DL and Swaminathan, S and Ravishanker, G and Withka, J and Srinivasan, J and Chantal Pr{\'e}vost and Louise-May, S and DiCapua, FM and Bolton, PH} } @article {1991|1762, title = {Molecular dynamics of polymers with fixed internal structure: Choice of models and methods}, journal = {Russ. J. Phys. Chem.}, volume = {65}, year = {1991}, pages = {2548{\textendash}2552}, author = {V. E. Dorofeyev and Alexey K Mazur} } @article {1991|1895, title = {THE USE OF ULTRAVIOLET RESONANCE RAMAN INTENSITIES TO TEST PROPOSED MOLECULAR-FORCE FIELDS FOR NUCLEIC-ACID BASES}, journal = {J. Comput. Chem.}, volume = {12}, number = {6}, year = {1991}, month = {jul}, pages = {731{\textendash}741}, doi = {10.1002/jcc.540120610}, author = {LAGANT, P and Philippe Derreumaux and VERGOTEN, G and PETICOLAS, W} } @article {1990|1929, title = {NORMAL-COORDINATE TREATMENT OF A NUCLEIC BASE PAIR MODEL IN ITS CRYSTALLINE STATE - 1-METHYLCYTOSINE-9-ETHYLGUANINE}, journal = {J. Raman Spectrosc.}, volume = {21}, number = {4}, year = {1990}, month = {apr}, pages = {215{\textendash}226}, doi = {10.1002/jrs.1250210402}, author = {LAGANT, P and VERGOTEN, G and Philippe Derreumaux and DHENNIN, R} } @article {1990|1894, title = {A VIBRATIONAL MOLECULAR-FORCE FIELD OF MODEL COMPOUNDS WITH BIOLOGICAL INTEREST .1. HARMONIC DYNAMICS OF CRYSTALLINE UREA AT 123-K}, journal = {J. Comput. Chem.}, volume = {11}, number = {5}, year = {1990}, month = {jun}, pages = {560{\textendash}568}, doi = {10.1002/jcc.540110504}, author = {Philippe Derreumaux and VERGOTEN, G and LAGANT, P} } @article {1989|1912, title = {CONFORMATIONAL STUDIES OF NEUROACTIVE LIGANDS .1. FORCE-FIELD AND VIBRATIONAL-SPECTRA OF CRYSTALLINE ACETYLCHOLINE}, journal = {J. Phys. Chem.}, volume = {93}, number = {4}, year = {1989}, month = {feb}, pages = {1338{\textendash}1350}, doi = {10.1021/j100341a033}, author = {Philippe Derreumaux and WILSON, KJ and VERGOTEN, G and PETICOLAS, WL} } @article {1989|1913, title = {CONFORMATIONAL STUDIES OF NEUROACTIVE LIGANDS .2. SOLUTION-STATE CONFORMATIONS OF ACETYLCHOLINE}, journal = {J. Phys. Chem.}, volume = {93}, number = {4}, year = {1989}, month = {feb}, pages = {1351{\textendash}1357}, doi = {10.1021/j100341a034}, author = {WILSON, KJ and Philippe Derreumaux and VERGOTEN, G and PETICOLAS, WL} } @article {1989|1796, title = {RAMAN-SPECTROSCOPY, MOLECULAR-FORCE FIELDS, AND THE DYNAMICS OF BIOLOGICAL MOLECULES}, journal = {Chemica Scripta}, volume = {29A}, year = {1989}, month = {sep}, pages = {113{\textendash}122}, author = {PETICOLAS, WL and WILSON, KJ and Philippe Derreumaux and VERGOTEN, G} } @article {1988|1597, title = {Analysis and parameter resolution in highly cooperative systems}, journal = {Biophys. Chem.}, volume = {30}, number = {2}, year = {1988}, month = {jun}, pages = {133{\textendash}141}, author = {Gill, S J and Connelly, P R and Di Cera, E and Charles H. Robert} } @article {1988|1590, title = {Nested allosteric interaction in tarantula hemocyanin revealed through the binding of oxygen and carbon monoxide}, journal = {Biochemistry}, volume = {27}, number = {18}, year = {1988}, month = {sep}, pages = {6901{\textendash}6908}, author = {Decker, H and Connelly, P R and Charles H. Robert and Gill, S J} } @article {1988|1625, title = {Uv Resonance Raman-spectra and Solution State Conformations of Cholinergic Neurotransmitters}, journal = {Biophys. J.}, volume = {53}, number = {2}, year = {1988}, month = {feb}, pages = {A287-A287}, author = {WILSON, K. J. and Philippe Derreumaux and VERGOTEN, G. and W. L. Peticolas} } @article {1987|1777, title = {Allosteric interpretation of the oxygen-binding reaction of human hemoglobin tetramers}, journal = {Biochemistry}, volume = {26}, number = {13}, year = {1987}, month = {jun}, pages = {4003{\textendash}4008}, author = {Di Cera, E and Robert, C H and Gill, S J} } @article {1987|1820, title = {Carbon dioxide and oxygen linkage in human hemoglobin tetramers}, journal = {J. Mol. Biol.}, volume = {196}, number = {4}, year = {1987}, month = {aug}, pages = {927{\textendash}934}, author = {Doyle, M L and Di Cera, E and Robert, C H and Gill, S J} } @inbook {1987|1429, title = {Nesting- An extension of the MWC model and its application to tarantula hemocyanin}, booktitle = {Invertebrate Oxygen Carriers}, year = {1987}, publisher = {Springer-Verlag}, organization = {Springer-Verlag}, address = {Berlin}, author = {Decker, H. and Robert, C. H. and Gill, S. J.} } @article {1987|1967, title = {Nesting: hierarchies of allosteric interactions}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {84}, number = {7}, year = {1987}, month = {apr}, pages = {1891{\textendash}1895}, author = {Robert, C H and Decker, H and Richey, B and Gill, S J and Wyman, J} } @article {1987|1592, title = {Oxygen binding constants for human hemoglobin tetramers}, journal = {Biochemistry}, volume = {26}, number = {13}, year = {1987}, month = {jun}, pages = {3995{\textendash}4002}, author = {Gill, S J and Di Cera, E and Doyle, M L and Bishop, G A and Charles H. Robert} } @article {1986|1602, title = {Cooperative free energies for nested allosteric models as applied to human hemoglobin}, journal = {Biophys. J.}, volume = {50}, number = {4}, year = {1986}, month = {oct}, pages = {747{\textendash}752}, author = {Gill, S J and Charles H. Robert and Coletta, M and Di Cera, E and Brunori, M} }