@article {2024, title = {A Perspective on the Prospective Use of AI in Protein Structure Prediction}, journal = {J Chem Inf Model}, volume = {64}, year = {2024}, month = {Jan}, pages = {26{\textendash}41}, author = {Versini, R. and Sritharan, S. and Aykac Fas, B. and Tubiana, T. and Aimeur, S. Z. and Henri, J. and Erard, M. and N{\"u}sse, O. and Andreani, J. and Baaden, M. and Fuchs, P. and Galochkina, T. and Chatzigoulas, A. and Cournia, Z. and Santuz, H. and S Sacquin-Mora and Taly, A.} } @article {2023|2164, title = {Molecular determinants of inhibition of UCP1-mediated respiratory uncoupling.}, journal = {Nat Commun}, volume = {14}, year = {2023}, month = {2023 May 05}, pages = {2594}, abstract = {

Brown adipose tissue expresses uncoupling protein 1 (UCP1), which dissipates energy as heat, making it a target for treating metabolic disorders. Here, we investigate how purine nucleotides inhibit respiration uncoupling by UCP1. Our molecular simulations predict that GDP and GTP bind UCP1 in the common substrate binding site in an upright orientation, where the base moiety interacts with conserved residues R92 and E191. We identify a triplet of uncharged residues, F88/I187/W281, forming hydrophobic contacts with nucleotides. In yeast spheroplast respiration assays, both I187A and W281A mutants increase the fatty acid-induced uncoupling activity of UCP1 and partially suppress the inhibition of UCP1 activity by nucleotides. The F88A/I187A/W281A triple mutant is overactivated by fatty acids even at high concentrations of purine nucleotides. In simulations, E191 and W281 interact with purine but not pyrimidine bases. These results provide a molecular understanding of the selective inhibition of UCP1 by purine nucleotides.

}, keywords = {Adipose Tissue, Brown, Fatty Acids, Ion Channels, Membrane Proteins, Mitochondrial Proteins, Purine Nucleotides, Saccharomyces cerevisiae, Uncoupling Protein 1}, issn = {2041-1723}, doi = {10.1038/s41467-023-38219-9}, author = {Gagelin, Antoine and Largeau, Corentin and Masscheleyn, Sandrine and Piel, Mathilde S and Calder{\'o}n-Mora, Daniel and Bouillaud, Fr{\'e}d{\'e}ric and J{\'e}r{\^o}me H{\'e}nin and Miroux, Bruno} } @article {2023|2165, title = {Unwrapping NPT Simulations to Calculate Diffusion Coefficients}, journal = {Journal of Chemical Theory and Computation}, volume = {19}, year = {2023}, pages = {3406{\textendash}3417}, doi = {10.1021/acs.jctc.3c00308}, url = {https://doi.org/10.1021/acs.jctc.3c00308}, author = {Jakob T{\'o}mas Bullerjahn and S{\"o}ren von B{\"u}low and Maziar Heidari and J{\'e}r{\^o}me H{\'e}nin and Gerhard Hummer} } @article {2022, title = {Between Two Walls: Modeling the Adsorption Behavior of β-Glucosidase A on Bare and SAM-Functionalized Gold Surfaces.}, journal = {Langmuir}, volume = {38}, year = {2022}, month = {2022 Feb 01}, pages = {1313-1323}, abstract = {

The efficient immobilization of enzymes on surfaces remains a complex but central issue in the biomaterials field, which requires us to understand this process at the atomic level. Using a multiscale approach combining all-atom molecular dynamics and coarse-grain Brownian dynamics simulations, we investigated the adsorption behavior of β-glucosidase A (βGA) on bare and self-assembled monolayer (SAM)-functionalized gold surfaces. We monitored the enzyme position and orientation during the molecular dynamics (MD) trajectories and measured the contacts it forms with both surfaces. While the adsorption process has little impact on the protein conformation, it can nonetheless perturb its mechanical properties and catalytic activity. Our results show that compared to the SAM-functionalized surface, the adsorption of βGA on bare gold is more stable, but less specific, and more likely to disrupt the enzyme\&$\#$39;s function. This observation emphasizes the fact that the structural organization of proteins at the solid interface is a key point when designing devices based on enzyme immobilization, as one must find an acceptable stability-activity trade-off.

}, issn = {1520-5827}, doi = {10.1021/acs.langmuir.1c01774}, author = {Bourassin, Nicolas and Barbault, Florent and Marc Baaden and S Sacquin-Mora} } @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|2159, title = {Design {\textendash} a new way to look at old molecules}, journal = {Journal of Integrative Bioinformatics}, volume = {19}, year = {2022}, pages = {20220020}, doi = {doi:10.1515/jib-2022-0020}, url = {https://doi.org/10.1515/jib-2022-0020}, author = {Davide Spalvieri and Anne-Marine Mauviel and Matthieu Lambert and Nicolas F{\'e}rey and S Sacquin-Mora and Matthieu Chavent and Marc Baaden} } @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|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 {2021|2155, title = {Modeling Perturbations in Protein Filaments at the Micro and Meso Scale Using NAMD and PTools/Heligeom}, journal = {Bio-protocol}, volume = {11}, year = {2021}, pages = {e4097}, abstract = {

Protein filaments are dynamic entities that respond to external stimuli by slightly or substantially modifying the internal binding geometries between successive protomers. This results in overall changes in the filament architecture, which are difficult to model due to the helical character of the system. Here, we describe how distortions in RecA nucleofilaments and their consequences on the filament-DNA and bound DNA-DNA interactions at different stages of the homologous recombination process can be modeled using the PTools/Heligeom software and subsequent molecular dynamics simulation with NAMD. Modeling methods dealing with helical macromolecular objects typically rely on symmetric assemblies and take advantage of known symmetry descriptors. Other methods dealing with single objects, such as MMTK or VMD, do not integrate the specificities of regular assemblies. By basing the model building on binding geometries at the protomer-protomer level, PTools/Heligeom frees the building process from a priori knowledge of the system topology and enables irregular architectures and symmetry disruption to be accounted for. doi: 10.21769/BioProtoc.4097

}, doi = {10.21769/BioProtoc.4097}, url = {www.bioprotocol.org/e4097}, author = {Boyer, B. and Laurent, B. and Robert, C. H. and Prevost, C.} } @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|2075, title = {Characterization of β-turns by electronic circular dichroism spectroscopy: a coupled molecular dynamics and time-dependent density functional theory computational study.}, journal = {Phys Chem Chem Phys}, volume = {22}, year = {2020}, month = {2020 Jan 21}, pages = {1611-1623}, abstract = {

Electronic circular dichroism is one of the most used spectroscopic techniques for peptide and protein structural characterization. However, while valuable experimental spectra exist for α-helix, β-sheet and random coil secondary structures, previous studies showed important discrepancies for β-turns, limiting their use as a reference for structural studies. In this paper, we simulated circular dichroism spectra for the best-characterized β-turns in peptides, namely types I, II, I\&$\#$39; and II\&$\#$39;. In particular, by combining classical molecular dynamics simulations and state-of-the-art quantum time-dependent density functional theory (with the polarizable embedding multiscale model) computations, two common electronic circular dichroism patterns were found for couples of β-turn types (namely, type I/type II\&$\#$39; and type II/type I\&$\#$39;), at first for a minimal di-peptide model (Ace-Ala-Ala-NHMe), but also for all sequences tested with non-aromatic residues in the central positions. On the other hand, as expected, aromatic substitution causes important perturbations to the previously found ECD patterns. Finally, by applying suitable approximations, these patterns were subsequently rationalized based on the exciton chirality rule. All these results provide useful predictions and pave the way for a possible experimental characterization of β-turns based on circular dichroism spectroscopy.

}, keywords = {Circular Dichroism, Computational Chemistry, Computer Simulation, Molecular Dynamics Simulation, Protein Conformation, beta-Strand, Protein Structure, Tertiary}, issn = {1463-9084}, doi = {10.1039/c9cp05776e}, author = {Migliore, Mattia and Bonvicini, Andrea and Tognetti, Vincent and Guilhaudis, Laure and Marc Baaden and Oulyadi, Hassan and Joubert, Laurent and S{\'e}galas-Milazzo, Isabelle} } @conference {2020|2100, title = {Computer Simulations Provide Guidance for Molecular Medicine Through Insights on Dynamics and Mechanisms at the Atomic Scale}, booktitle = {7th International Conference on the Development of Biomedical Engineering in Vietnam (BME7)}, year = {2020}, publisher = {Springer}, organization = {Springer}, address = {Singapore}, abstract = {

Computer simulations provide crucial insights and rationales for the design of molecular approaches in medicine. Several case studies illustrate how molecular model building and molecular dynamics simulations of complex molecular assemblies such as membrane proteins help in that process. Important aspects relate to build relevant molecular models with and without a crystal structure, to model membrane aggregates, then to link (dynamic) models to function, and finally to understand key disease-triggering phenomena such as aggregation. Through selected examples\—including key signaling pathways in neurotransmission\—the links between a molecular-level understanding of biological mechanisms and original approaches to treat disease conditions will be illuminated. Such treatments may be symptomatic, e.g. by better understanding the function and pharmacology of macromolecular key players, or curative, e.g. through molecular inhibition of disease-inducing molecular processes.

}, keywords = {Model building, molecular dynamics, Molecular mechanisms of disease}, isbn = {9789811358593}, doi = {10.1007/978-981-13-5859-3_47}, author = {Marc Baaden}, editor = {Van Toi, Vo and Le, Trung Quoc and Ngo, Hoan Thanh and Nguyen, Thi-Hiep} } @article {2020|2144, title = {Implicit Modeling of the Impact of Adsorption on Solid Surfaces for Protein Mechanics and Activity with a Coarse-Grained Representation}, journal = {J Phys Chem B}, volume = {124}, year = {2020}, month = {Oct}, pages = {8516{\textendash}8523}, author = {Bourassin, N. and Marc Baaden and Lojou, E. and S Sacquin-Mora} } @article {2020, title = {Protein Interaction Energy Landscapes are Shaped by Functional and also Non-functional Partners.}, journal = {J Mol Biol}, volume = {432}, year = {2020}, month = {2020 Feb 14}, pages = {1183-1198}, abstract = {

In the crowded cell, a strong selective pressure operates on the proteome to limit the competition between functional and non-functional protein-protein interactions. We developed an original theoretical framework in order to interrogate how this competition constrains the behavior of proteins with respect to their partners or random encounters. Our theoretical framework relies on a two-dimensional (2D) representation of interaction energy landscapes, with 2D energy maps, which reflect in a synthetic way the spatial distribution of the interaction propensity of a protein surface for another protein. We realized the interaction propensity mapping of proteins\&$\#$39; surfaces in interaction with functional and arbitrary partners and asked whether the distribution of their interaction propensity is conserved during evolution. Therefore, we performed several thousands of cross-docking simulations to systematically characterize the energy landscapes of 103 proteins interacting with different sets of homologs, corresponding to their functional partner\&$\#$39;s family or arbitrary protein families. Then, we systematically compared the energy maps resulting from the docking of each protein with the different protein families of the dataset. Strikingly, we show that the interaction propensity not only of the binding sites but also of the rest of the surface is conserved for docking partners belonging to the same protein family. Interestingly, this observation holds for docked proteins corresponding to true but also arbitrary partners. Our theoretical framework enables the characterization of the energy behavior of a protein in interaction with hundreds of proteins and opens the way for the characterization of the behavior of proteins in a specific environment.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2019.12.047}, author = {Schweke, Hugo and Mucchielli, Marie-H{\'e}l{\`e}ne and S Sacquin-Mora and Bei, Wanying and Lopes, Anne} } @article {2020|2142, title = {Scalable molecular dynamics on CPU and GPU architectures with NAMD}, journal = {The Journal of Chemical Physics}, volume = {153}, year = {2020}, chapter = {044130}, abstract = {

NAMD is a molecular dynamics program designed for high-performance simulations of very large biological objects on CPU- and GPU-based architectures. NAMD offers scalable performance on petascale parallel supercomputers consisting of hundreds of thousands of cores, as well as on inexpensive commodity clusters commonly found in academic environments. It is written in C++ and leans on Charm++ parallel objects for optimal performance on low-latency architectures. NAMD is a versatile, multipurpose code that gathers state-of-the-art algorithms to carry out simulations in apt thermodynamic ensembles, using the widely popular CHARMM, AMBER, OPLS, and GROMOS biomolecular force fields. Here, we review the main features of NAMD that allow both equilibrium and enhanced-sampling molecular dynamics simulations with numerical efficiency. We describe the underlying concepts utilized by NAMD and their implementation, most notably for handling long-range electrostatics; controlling the temperature, pressure, and pH; applying external potentials on tailored grids; leveraging massively parallel resources in multiple-copy simulations; and hybrid quantum-mechanical/molecular-mechanical descriptions. We detail the variety of options offered by NAMD for enhanced-sampling simulations aimed at determining free-energy differences of either alchemical or geometrical transformations and outline their applicability to specific problems. Last, we discuss the roadmap for the development of NAMD and our current efforts toward achieving optimal performance on GPU-based architectures, for pushing back the limitations that have prevented biologically realistic billion-atom objects to be fruitfully simulated, and for making large-scale simulations less expensive and easier to set up, run, and analyze. NAMD is distributed free of charge with its source code at www.ks.uiuc.edu.

}, keywords = {NAMD}, doi = {10.1063/5.0014475}, url = {https://aip.scitation.org/doi/10.1063/5.0014475}, author = {James Phillips and David Hardy and Julio Maia and John Stone and Joao Ribeiro and Rafael Bernardi and Ronak Buch and Giacomo Fiorin and J{\'e}r{\^o}me H{\'e}nin and Wei Jiang and Ryan McGreevy and Melo, Marcelo Cardoso dos Reis and Brian Radak and Robert Skeel and Abhishek Singharoy and Yi Wang and Benoit Roux and Aleksei Aksimentiev and Zan Luthey-Schulten and Laxmikant Kale and Klaus Schulten and Christophe Chipot and Emad Tajkhorshid} } @article {2020|2098, title = {Scruter les mol{\'e}cules en r{\'e}alit{\'e} virtuelle, pour quoi faire ?}, journal = {L{\textquoteright}Actualit{\'e} Chimique}, year = {2020}, pages = {23{\textendash}26}, abstract = {

Les repr{\'e}sentations des mol{\'e}cules ont pris une place importante dans la communication d\’id{\'e}es, la g{\'e}n{\'e}ration d\’hypoth{\`e}ses sur les m{\'e}canismes biologiques et l\’analyse de simulations mol{\'e}culaires. Pourtant, les dispositifs pour les observer et les manipuler restent souvent cantonn{\'e}s aux deux dimensions des {\'e}crans et {\`a} l\’interaction limit{\'e}e d\’une souris et d\’un clavier. D\’autres solutions plus performantes et {\`a} port{\'e}e de tous existent, notamment avec les derni{\`e}res {\'e}volutions de la r{\'e}alit{\'e} virtuelle pour le grand public. Des adaptations sont n{\'e}anmoins n{\'e}cessaires pour b{\'e}n{\'e}ficier pleinement des avantages li{\'e}s {\`a} l\’utilisation de la r{\'e}alit{\'e} virtuelle pour la visualisation scientifique. Cet article pr{\'e}sente quelques exemples r{\'e}alis{\'e}s avec le logiciel UnityMol. En plus des applications directes dans l\’enseignement, le changement de paradigme d\’interaction et la perception accrue de la profondeur et des formes des mol{\'e}cules biologiques facilitent d{\`e}s {\`a} pr{\'e}sent la compr{\'e}hension de ces syst{\`e}mes complexes et am{\`e}neront certainement {\`a} la d{\'e}couverte de nouveaux savoirs scientifiques.

}, issn = {0151-9093}, url = {http://www.lactualitechimique.org/Scruter-les-molecules-en-realite-virtuelle-pour-quoi-faire}, author = {Martinez, Xavier and Marc Baaden} } @article {2020|2077, title = {Visualizing biomolecular electrostatics in virtual reality with UnityMol-APBS.}, journal = {Protein Sci}, volume = {29}, year = {2020}, month = {2020 Jan}, pages = {237-246}, abstract = {

Virtual reality is a powerful tool with the ability to immerse a user within a completely external environment. This immersion is particularly useful when visualizing and analyzing interactions between small organic molecules, molecular inorganic complexes, and biomolecular systems such as redox proteins and enzymes. A common tool used in the biomedical community to analyze such interactions is the Adaptive Poisson-Boltzmann Solver (APBS) software, which was developed to solve the equations of continuum electrostatics for large biomolecular assemblages. Numerous applications exist for using APBS in the biomedical community including analysis of protein ligand interactions and APBS has enjoyed widespread adoption throughout the biomedical community. Currently, typical use of the full APBS toolset is completed via the command line followed by visualization using a variety of two-dimensional external molecular visualization software. This process has inherent limitations: visualization of three-dimensional objects using a two-dimensional interface masks important information within the depth component. Herein, we have developed a single application, UnityMol-APBS, that provides a dual experience where users can utilize the full range of the APBS toolset, without the use of a command line interface, by use of a simple graphical user interface (GUI) for either a standard desktop or immersive virtual reality experience.

}, issn = {1469-896X}, doi = {10.1002/pro.3773}, author = {Laureanti, Joseph and Brandi, Juan and Offor, Elvis and Engel, David and Rallo, Robert and Ginovska, Bojana and Martinez, Xavier and Marc Baaden and Baker, Nathan A} } @article {2020|2074, title = {Visualizing protein structures - tools and trends.}, journal = {Biochem Soc Trans}, year = {2020}, month = {2020 Mar 20}, abstract = {

Molecular visualization is fundamental in the current scientific literature, textbooks and dissemination materials. It provides an essential support for presenting results, reasoning on and formulating hypotheses related to molecular structure. Tools for visual exploration of structural data have become easily accessible on a broad variety of platforms thanks to advanced software tools that render a great service to the scientific community. These tools are often developed across disciplines bridging computer science, biology and chemistry. This mini-review was written as a short and compact overview for scientists who need to visualize protein structures and want to make an informed decision which tool they should use. Here, we first describe a few \&$\#$39;Swiss Army knives\&$\#$39; geared towards protein visualization for everyday use with an existing large user base, then focus on more specialized tools for peculiar needs that are not yet as broadly known. Our selection is by no means exhaustive, but reflects a diverse snapshot of scenarios that we consider informative for the reader. We end with an account of future trends and perspectives.

}, issn = {1470-8752}, doi = {10.1042/BST20190621}, author = {Martinez, Xavier and Chavent, Matthieu and Marc Baaden} } @article {2019|2060, title = {Conformational Stability Adaptation of a Double-Stranded RNA-Binding Domain to Transfer RNA Ligand.}, journal = {Biochemistry}, volume = {58}, year = {2019}, month = {2019 May 21}, pages = {2463-2473}, abstract = {

The double-stranded RNA-binding domain (dsRBD) is a broadly distributed domain among RNA-maturing enzymes. Although this domain recognizes dsRNA\&$\#$39;s structures via a conserved canonical structure adopting an α-βββ-α topology, several dsRBDs can accommodate discrete structural extensions expanding further their functional repertoire. How these structural elements engage cooperative communications with the canonical structure and how they contribute to the dsRBD\&$\#$39;s overall folding are poorly understood. Here, we addressed these issues using the dsRBD of human dihydrouridine synthase-2 (hDus2) (hDus2-dsRBD) as a model. This dsRBD harbors N- and C-terminal extensions, the former being directly involved in the recognition of tRNA substrate of hDus2. These extensions engage residues that form a long-range hydrophobic network (LHN) outside the RNA-binding interface. We show by coarse-grain Brownian dynamics that the Nt-extension and its residues F359 and Y364 rigidify the major folding nucleus of the canonical structure via an indirect effect. hDus2-dsRBD unfolds following a two-state cooperative model, whereas both F359A and Y364A mutants, designed to destabilize this LHN, unfold irreversibly. Structural and computational analyses show that these mutants are unstable due to an increase in the dynamics of the two extensions favoring solvent exposure of α2-helix and weakening the main folding nucleus rigidity. This LHN appears essential for maintaining a thermodynamic stability of the overall system and eventually a functional conformation for tRNA recognition. Altogether, our findings suggest that functional adaptability of extended dsRBDs is promoted by a cooperative hydrophobic coupling between the extensions acting as effectors and the folding nucleus of the canonical structure.

}, issn = {1520-4995}, doi = {10.1021/acs.biochem.9b00111}, author = {Bou-Nader, Charles and Pecqueur, Ludovic and Barraud, Pierre and Fontecave, Marc and Tisn{\'e}, Carine and S Sacquin-Mora and Hamdane, Djemel} } @article {2019|2076, title = {Glutathionylation primes soluble glyceraldehyde-3-phosphate dehydrogenase for late collapse into insoluble aggregates.}, journal = {Proc Natl Acad Sci U S A}, volume = {116}, year = {2019}, month = {2019 12 17}, pages = {26057-26065}, abstract = {

Protein aggregation is a complex physiological process, primarily determined by stress-related factors revealing the hidden aggregation propensity of proteins that otherwise are fully soluble. Here we report a mechanism by which glycolytic glyceraldehyde-3-phosphate dehydrogenase of (AtGAPC1) is primed to form insoluble aggregates by the glutathionylation of its catalytic cysteine (Cys149). Following a lag phase, glutathionylated AtGAPC1 initiates a self-aggregation process resulting in the formation of branched chains of globular particles made of partially misfolded and totally inactive proteins. GSH molecules within AtGAPC1 active sites are suggested to provide the initial destabilizing signal. The following removal of glutathione by the formation of an intramolecular disulfide bond between Cys149 and Cys153 reinforces the aggregation process. Physiological reductases, thioredoxins and glutaredoxins, could not dissolve AtGAPC1 aggregates but could efficiently contrast their growth. Besides acting as a protective mechanism against overoxidation, S-glutathionylation of AtGAPC1 triggers an unexpected aggregation pathway with completely different and still unexplored physiological implications.

}, issn = {1091-6490}, doi = {10.1073/pnas.1914484116}, author = {Zaffagnini, Mirko and Marchand, Christophe H and Malferrari, Marco and Murail, Samuel and Bonacchi, Sara and Genovese, Damiano and Montalti, Marco and Venturoli, Giovanni and Falini, Giuseppe and Marc Baaden and Lemaire, St{\'e}phane D and Fermani, Simona and Trost, Paolo} } @article {2019|2080, title = {Highlights from the Faraday Discussion on Artificial Water Channels, Glasgow, UK.}, journal = {Chem Commun (Camb)}, volume = {55}, year = {2019}, month = {2019 Apr 07}, pages = {3853-3858}, issn = {1364-548X}, doi = {10.1039/c9cc90112d}, author = {Barboiu, Mihail and Kumar, Manish and Marc Baaden and Gale, Philip A and Hinds, Bruce J} } @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|2079, title = {Molecular Graphics: Bridging Structural Biologists and Computer Scientists.}, journal = {Structure}, volume = {27}, year = {2019}, month = {2019 11 05}, pages = {1617-1623}, abstract = {

Visualization of molecular structures is one of the most common tasks carried out by structural biologists, typically using software, such as Chimera, COOT, PyMOL, or VMD. In this Perspective article, we outline how past developments in computer graphics and data visualization have expanded the understanding of biomolecular function, and we summarize recent advances that promise to further transform structural biology. We also highlight how progress in molecular graphics has been impeded by communication barriers between two communities: the computer scientists driving these advances, and the structural and computational biologists who stand to benefit. By pointing to canonical papers and explaining technical progress underlying new graphical developments in simple terms, we aim to improve communication between these communities; this, in turn, would help shape future developments in molecular graphics.

}, issn = {1878-4186}, doi = {10.1016/j.str.2019.09.001}, author = {Martinez, Xavier and Krone, Michael and Alharbi, Naif and Rose, Alexander S and Laramee, Robert S and O{\textquoteright}Donoghue, Sean and Marc Baaden and Chavent, Matthieu} } @article {2019|2068, title = {Molecular modelling as the spark for active learning approaches for interdisciplinary biology teaching}, journal = {Interface focus}, volume = {9}, year = {2019}, pages = {20180065}, author = {Antoine Taly and Nitti, Francesco and Marc Baaden and Pasquali, S} } @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|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} } @conference {2019|2099, title = {QuickSES: A Library for Fast Computation of Solvent Excluded Surfaces}, booktitle = {Workshop on Molecular Graphics and Visual Analysis of Molecular Data}, year = {2019}, publisher = {The Eurographics Association}, organization = {The Eurographics Association}, isbn = {978-3-03868-085-7}, doi = {10.2312/molva.20191095}, author = {Martinez, Xavier and Krone, Michael and Marc Baaden}, editor = {Byska, Jan and Krone, Michael and Sommer, Bj{\"o}rn} } @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|2081, title = {Visualizing Biological Membrane Organization and Dynamics.}, journal = {J Mol Biol}, volume = {431}, year = {2019}, month = {2019 05 03}, pages = {1889-1919}, abstract = {

Biological membranes are fascinating. Santiago Ram{\'o}n y Cajal, who received the Nobel prize in 1906 together with Camillo Golgi for their work on the nervous system, wrote \"[\…]in the study of this membrane[\…] I felt more profoundly than in any other subject of study the shuddering sensation of the unfathomable mystery of life\". The visualization and conceptualization of these biological objects have profoundly shaped many aspects of modern biology, drawing inspiration from experiments, computer simulations, and the imagination of scientists and artists. The aim of this review is to provide a fresh look on current ideas of biological membrane organization and dynamics by discussing selected examples across fields.

}, keywords = {Animals, Cell Membrane, Humans, Lipid Bilayers, Microscopy, Atomic Force, Microscopy, Electron, Transmission, Molecular Dynamics Simulation}, issn = {1089-8638}, doi = {10.1016/j.jmb.2019.02.018}, author = {Marc Baaden} } @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} } @article {2018|2086, title = {Analyzing protein topology based on Laguerre tessellation of a pore-traversing water network.}, journal = {Sci Rep}, volume = {8}, year = {2018}, month = {2018 09 10}, pages = {13540}, abstract = {

Given the tight relation between protein structure and function, we present a set of methods to analyze protein topology, implemented in the VLDP program, relying on Laguerre space partitions built from series of molecular dynamics snapshots. The Laguerre partition specifies inter-atomic contacts, formalized in graphs. The deduced properties are the existence and count of water aggregates, possible passage ways and constrictions, the structure, connectivity, stability and depth of the water network. As a test-case, the membrane protein FepA is investigated in its full environment, yielding a more precise description of the protein surface. Inside FepA, the solvent splits into isolated clusters and an intricate network connecting both sides of the lipid bilayer. The network is dynamic, connections set on and off, occasionally substantially relocating traversing paths. Subtle differences are detected between two forms of FepA, ligand-free and complexed with its natural iron carrier, the enterobactin. The complexed form has more constricted and more centered openings in the upper part whereas, in the lower part, constriction is released: two main channels between the plug and barrel lead directly to the periplasm. Reliability, precision and the variety of topological features are the main interest of the method.

}, keywords = {Bacterial Outer Membrane Proteins, Carrier Proteins, Enterobactin, Molecular Dynamics Simulation, Protein Stability, Protein Structure, Secondary, Receptors, Cell Surface, Structure-Activity Relationship, Water}, issn = {2045-2322}, doi = {10.1038/s41598-018-31422-5}, author = {Esque, J{\'e}r{\'e}my and Sansom, Mark S P and Marc Baaden and Oguey, Christophe} } @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|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|2088, title = {From Virtual Reality to Immersive Analytics in Bioinformatics.}, journal = {J Integr Bioinform}, volume = {15}, year = {2018}, month = {2018 Jul 09}, abstract = {

Bioinformatics-related research produces huge heterogeneous amounts of data. This wealth of information includes data describing metabolic mechanisms and pathways, proteomics, transcriptomics, and metabolomics. Often, the visualization and exploration of related structural - usually molecular - data plays an important role in the aforementioned contexts. For decades, virtual reality (VR)-related technologies were developed and applied to Bioinformatics problems. Often, these approaches provide \"just\" visual support of the analysis, e.g. in the case of exploring and interacting with a protein on a 3D monitor and compatible interaction hardware. Moreover, in the past these approaches were limited to cost-intensive professional visualization facilities. The advent of new affordable, and often mobile technologies, provides high potential for using similar approaches on a regular basis for daily research. Visual Analytics is successfully being used for several years to analyze complex and heterogeneous datasets. Immersive Analytics combines these approaches now with new immersive and interactive technologies. This publication provides a short overview of related technologies, their history and Bioinformatics-related approaches. Six new applications on the path from VR to Immersive Analytics are being introduced and discussed.

}, keywords = {Computer Graphics, Imaging, Three-Dimensional, Molecular Conformation, Proteins, Software, User-Computer Interface, Virtual Reality}, issn = {1613-4516}, doi = {10.1515/jib-2018-0043}, author = {Sommer, Bj{\"o}rn and Marc Baaden and Krone, Michael and Woods, Andrew} } @article {2018|2094, title = {Holding the Nucleosome Together: A Quantitative Description of the DNA-Histone Interface in Solution.}, journal = {J Chem Theory Comput}, volume = {14}, year = {2018}, month = {2018 Feb 13}, pages = {1045-1058}, abstract = {

The nucleosome is the fundamental unit of eukaryotic genome packaging in the chromatin. In this complex, the DNA wraps around eight histone proteins to form a superhelical double helix. The resulting bending, stronger than anything observed in free DNA, raises the question of how such a distortion is stabilized by the proteic and solvent environments. In this work, the DNA-histone interface in solution was exhaustively analyzed from nucleosome structures generated by molecular dynamics. An original Voronoi tessellation technique, measuring the topology of interacting elements without any empirical or subjective adjustment, was used to characterize the interface in terms of contact area and occurrence. Our results revealed an interface more robust than previously known, combining extensive, long-lived nonelectrostatic and electrostatic interactions between DNA and both structured and unstructured histone regions. Cation accumulation makes the proximity of juxtaposed DNA gyres in the superhelix possible by shielding the strong electrostatic repulsion of the charged phosphate groups. Overall, this study provides new insights on the nucleosome cohesion, explaining how DNA distortions can be maintained in a nucleoprotein complex.

}, keywords = {DNA, Histones, Molecular Dynamics Simulation, Nucleosomes, Solutions, Static Electricity}, issn = {1549-9626}, doi = {10.1021/acs.jctc.7b00936}, author = {Elbahnsi, Ahmad and Retureau, Romain and Marc Baaden and Hartmann, Brigitte and Oguey, Christophe} } @article {2018|2087, title = {The major β-catenin/E-cadherin junctional binding site is a primary molecular mechano-transductor of differentiation .}, journal = {Elife}, volume = {7}, year = {2018}, month = {2018 07 19}, abstract = {

, the primary molecular mechanotransductive events mechanically initiating cell differentiation remain unknown. Here we find the molecular stretching of the highly conserved Y654-β-catenin-D665-E-cadherin binding site as mechanically induced by tissue strain. It triggers the increase of accessibility of the Y654 site, target of the Src42A kinase phosphorylation leading to irreversible unbinding. Molecular dynamics simulations of the β-catenin/E-cadherin complex under a force mimicking a 6 pN physiological mechanical strain predict a local 45\% stretching between the two α-helices linked by the site and a 15\% increase in accessibility of the phosphorylation site. Both are quantitatively observed using FRET lifetime imaging and non-phospho Y654 specific antibody labelling, in response to the mechanical strains developed by endogenous and magnetically mimicked early mesoderm invagination of gastrulating embryos. This is followed by the predicted release of 16\% of β-catenin from junctions, observed in FRAP, which initiates the mechanical activation of the β-catenin pathway process.

}, keywords = {Amino Acid Sequence, Animals, Armadillo Domain Proteins, Binding Sites, Cadherins, Cell Differentiation, Drosophila melanogaster, Drosophila Proteins, Fluorescence Resonance Energy Transfer, Mechanotransduction, Cellular, Molecular Dynamics Simulation, Phosphorylation, Protein Binding, Protein Conformation, Proto-Oncogene Proteins pp60(c-src), Sequence Homology, Transcription Factors}, issn = {2050-084X}, doi = {10.7554/eLife.33381}, author = {R{\"o}per, Jens-Christian and Mitrossilis, D{\'e}mosth{\`e}ne and Guillaume Stirnemann and Waharte, Fran{\c c}ois and Brito, Isabel and Fernandez-Sanchez, Maria-Elena and Marc Baaden and Salamero, Jean and Farge, Emmanuel} } @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} } @inbook {2018|2084, title = {The modelling and enhancement of water hydrodynamics: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {273-285}, issn = {1364-5498}, doi = {10.1039/c8fd90021c}, author = {Marc Baaden and Borthakur, Manash Pratim and Casanova, Serena and Coalson, Rob and Freger, Viatcheslav and Gonzalez, Miguel and G{\'o}ra, Artur and Hinds, Bruce and Hirunpinyopas, Wisit and Hummer, Gerhard and Kumar, Manish and Lynch, Charlotte and Murail, Samuel and Noy, Aleksandr and Sansom, Mark and Song, Qilei and Vashisth, Harish and V{\"o}gele, Martin} } @article {2018|2092, title = {Oriented chiral water wires in artificial transmembrane channels.}, journal = {Sci Adv}, volume = {4}, year = {2018}, month = {2018 03}, pages = {eaao5603}, abstract = {

Aquaporins (AQPs) feature highly selective water transport through cell membranes, where the dipolar orientation of structured water wires spanning the AQP pore is of considerable importance for the selective translocation of water over ions. We recently discovered that water permeability through artificial water channels formed by stacked imidazole I-quartet superstructures increases when the channel water molecules are highly organized. Correlating water structure with molecular transport is essential for understanding the underlying mechanisms of (fast) water translocation and channel selectivity. Chirality adds another factor enabling unique dipolar oriented water structures. We show that water molecules exhibit a dipolar oriented wire structure within chiral I-quartet water channels both in the solid state and embedded in supported lipid bilayer membranes (SLBs). X-ray single-crystal structures show that crystallographic water wires exhibit dipolar orientation, which is unique for chiral I-quartets. The integration of I-quartets into SLBs was monitored with a quartz crystal microbalance with dissipation, quantizing the amount of channel water molecules. Nonlinear sum-frequency generation vibrational spectroscopy demonstrates the first experimental observation of dipolar oriented water structures within artificial water channels inserted in bilayer membranes. Confirmation of the ordered confined water is obtained via molecular simulations, which provide quantitative measures of hydrogen bond strength, connectivity, and the stability of their dipolar alignment in a membrane environment. Together, uncovering the interplay between the dipolar aligned water structure and water transport through the self-assembled I-quartets is critical to understanding the behavior of natural membrane channels and will accelerate the systematic discovery for developing artificial water channels for water desalting.

}, issn = {2375-2548}, doi = {10.1126/sciadv.aao5603}, author = {Kocsis, Istvan and Sorci, Mirco and Vanselous, Heather and Murail, Samuel and Sanders, Stephanie E and Licsandru, Erol and Legrand, Yves-Marie and van der Lee, Arie and Marc Baaden and Petersen, Poul B and Belfort, Georges and Barboiu, Mihail} } @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|2135, title = {Segmentation and the Entropic Elasticity of Modular Proteins}, journal = {J Phys Chem Lett}, volume = {9}, year = {2018}, month = {Aug}, pages = {4707-4713}, abstract = {

Single-molecule force spectroscopy utilizes polyproteins, which are composed of tandem modular domains, to study their mechanical and structural properties. Under the application of external load, the polyproteins respond by unfolding and refolding domains to acquire the most favored extensibility. However, unlike single-domain proteins, the sequential unfolding of the each domain modifies the free energy landscape (FEL) of the polyprotein nonlinearly. Here we use force-clamp (FC) spectroscopy to measure unfolding and collapse-refolding dynamics of polyubiquitin and poly(I91). Their reconstructed unfolding FEL involves hundreds of kB T in accumulating work performed against conformational entropy, which dwarfs the \∼30 kB T that is typically required to overcome the free energy difference of unfolding. We speculate that the additional entropic energy caused by segmentation of the polyprotein to individual proteins plays a crucial role in defining the \"shock absorber\" properties of elastic proteins such as the giant muscle protein titin.

}, doi = {10.1021/acs.jpclett.8b01925}, author = {Berkovich, Ronen and Fernandez, Vicente I and Guillaume Stirnemann and Valle-Orero, Jessica and Fernandez, Julio M} } @article {2018|2089, title = {Semantics for an Integrative and Immersive Pipeline Combining Visualization and Analysis of Molecular Data.}, journal = {J Integr Bioinform}, volume = {15}, year = {2018}, month = {2018 Jul 09}, abstract = {

The advances made in recent years in the field of structural biology significantly increased the throughput and complexity of data that scientists have to deal with. Combining and analyzing such heterogeneous amounts of data became a crucial time consumer in the daily tasks of scientists. However, only few efforts have been made to offer scientists an alternative to the standard compartmentalized tools they use to explore their data and that involve a regular back and forth between them. We propose here an integrated pipeline especially designed for immersive environments, promoting direct interactions on semantically linked 2D and 3D heterogeneous data, displayed in a common working space. The creation of a semantic definition describing the content and the context of a molecular scene leads to the creation of an intelligent system where data are (1) combined through pre-existing or inferred links present in our hierarchical definition of the concepts, (2) enriched with suitable and adaptive analyses proposed to the user with respect to the current task and (3) interactively presented in a unique working environment to be explored.

}, keywords = {Computer Graphics, Humans, Imaging, Three-Dimensional, Models, Structural, Semantics, Software, Statistics as Topic, User-Computer Interface}, issn = {1613-4516}, doi = {10.1515/jib-2018-0004}, author = {Trellet, Mikael and Nicolas F{\'e}rey and Floty{\'n}ski, Jakub and Marc Baaden and Bourdot, Patrick} } @article {2018|2059, title = {A Streamlined, General Approach for Computing Ligand Binding Free Energies and Its Application to GPCR-Bound Cholesterol.}, journal = {Journal of Chemical Theory and Computation}, volume = {14}, year = {2018}, pages = {6560{\textendash}6573}, abstract = {

The theory of receptor-ligand binding equilibria has long been well-established in biochemistry, and was primarily constructed to describe dilute aqueous solutions. Accordingly, few computational approaches have been developed for making quantitative predictions of binding probabilities in environments other than dilute isotropic solution. Existing techniques, ranging from simple automated docking procedures to sophisticated thermodynamics-based methods, have been developed with soluble proteins in mind. Biologically and pharmacologically relevant protein-ligand interactions often occur in complex environments, including lamellar phases like membranes and crowded, nondilute solutions. Here, we revisit the theoretical bases of ligand binding equilibria, avoiding overly specific assumptions that are nearly always made when describing receptor-ligand binding. Building on this formalism, we extend the asymptotically exact Alchemical Free Energy Perturbation technique to quantifying occupancies of sites on proteins in a complex bulk, including phase-separated, anisotropic, or nondilute solutions, using a thermodynamically consistent and easily generalized approach that resolves several ambiguities of current frameworks. To incorporate the complex bulk without overcomplicating the overall thermodynamic cycle, we simplify the common approach for ligand restraints by using a single distance-from-bound-configuration (DBC) ligand restraint during AFEP decoupling from protein. DBC restraints should be generalizable to binding modes of most small molecules, even those with strong orientational dependence. We apply this approach to compute the likelihood that membrane cholesterol binds to known crystallographic sites on three GPCRs (β -adrenergic, 5HT-2B, and μ-opioid) at a range of concentrations. Nonideality of cholesterol in a binary cholesterol:phosphatidylcholine (POPC) bilayer is characterized and consistently incorporated into the interpretation. We find that the three sites exhibit very different affinities for cholesterol: The site on the adrenergic receptor is predicted to be high affinity, with 50\% occupancy for 1:10 CHOL:POPC mixtures. The sites on the 5HT-2B and μ-opioid receptor are predicted to be lower affinity, with 50\% occupancy for 1:10 CHOL:POPC and 1:10 CHOL:POPC, respectively. These results could not have been predicted from the crystal structures alone.

}, issn = {1549-9626}, doi = {10.1021/acs.jctc.8b00447}, author = {Salari, Reza and Joseph, Thomas and Lohia, Ruchi and J{\'e}r{\^o}me H{\'e}nin and Brannigan, Grace} } @inbook {2018|2083, title = {Structure and function of natural proteins for water transport: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {83-95}, keywords = {Molecular Structure, Proteins, Water}, issn = {1364-5498}, doi = {10.1039/c8fd90019a}, author = {Marc Baaden and Barboiu, Mihail and Bill, Roslyn M and Casanova, Serena and Chen, Chun-Long and Conner, Matthew and Freger, Viatcheslav and Gong, Bing and G{\'o}ra, Artur and Hinds, Bruce and Horner, Andreas and Hummer, Gerhard and Kumar, Manish and Lokesh, Mahesh and Mitra, Sushanta and Noy, Aleksandr and Pohl, Peter and Sadet, Aude and Sansom, Mark and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish} } @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|2090, title = {Water permeation across artificial I-quartet membrane channels: from structure to disorder.}, journal = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {125-148}, abstract = {

Artificial water channels (AWCs) have been designed for water transport across membranes with the aim to mimic the high water permeability observed for biological systems such as aquaporins (\∼108-109 water molecules per s per channel), as well as their selectivity to reject ion permeation at the same time. Recent works on designed self-assembling alkylureido-ethylimidazole compounds forming imidazole-quartet channels (I-quartets), have shown both high water permeability and total ionic-rejection. I-quartets are thus promising candidates for further development of AWCs. However, the molecular mechanism of water permeation as well as I-quartet organization and stability in a membrane environment need to be fully understood to guide their optimal design. Here, we use a wide range of all-atom molecular dynamics (MD) simulations and their analysis to understand the structure/activity relationships of the I-quartet channels. Four different types with varying alkyl chain length or chirality have been studied in a complex fully hydrated lipid bilayer environment at both microsecond and nanosecond scale. Microsecond simulations show two distinct behaviors; (i) two out of four systems maintain chiral dipolar oriented water wires, but also undergo a strong reorganization of the crystal shape, (ii) the two other I-quartet channels completely lose the initial organization, nonetheless keeping a water transport activity. Short MD simulations with higher time resolution were conducted to characterize the dynamic properties of water molecules in these model channels and provided a detailed hypothesis on the molecular mechanism of water permeation. The ordered confined water was characterized with quantitative measures of hydrogen-bond life-time and single particle dynamics, showing variability among I-quartet channels. We will further discuss the underlying assumptions, currently based on self-aggregation simulations and crystal patches embedded in lipid bilayer simulations and attempt to describe possible alternative approaches to computationally capture the water permeation mechanism and the self-assembly process of these AWCs.

}, issn = {1364-5498}, doi = {10.1039/c8fd00046h}, author = {Murail, Samuel and Vasiliu, Tudor and Neamtu, Andrei and Barboiu, Mihail and Sterpone, Fabio and Marc Baaden} } @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} } @conference {2017|2101, title = {Molecular Visualization of Computational Biology Data: A Survey of Surveys}, booktitle = {EuroVis 2017 - Short Papers}, year = {2017}, publisher = {The Eurographics Association}, organization = {The Eurographics Association}, isbn = {978-3-03868-043-7}, doi = {10.2312/eurovisshort.20171146}, author = {Alharbi, Naif and Alharbi, Mohammad and Martinez, Xavier and Krone, Michael and Rose, Alexander S. and Marc Baaden and Laramee, Robert S. and Chavent, Matthieu}, editor = {Barbora Kozlikova and Tobias Schreck and Thomas Wischgoll} } @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|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|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|2026, title = {Tailoring protein nanomechanics with chemical reactivity}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {Jun}, pages = {15658}, abstract = {

The nanomechanical properties of elastomeric proteins determine the elasticity of a variety of tissues. A widespread natural tactic to regulate protein extensibility lies in the presence of covalent disulfide bonds, which significantly enhance protein stiffness. The prevalent in vivo strategy to form disulfide bonds requires the presence of dedicated enzymes. Here we propose an alternative chemical route to promote non-enzymatic oxidative protein folding via disulfide isomerization based on naturally occurring small molecules. Using single-molecule force-clamp spectroscopy, supported by DFT calculations and mass spectrometry measurements, we demonstrate that subtle changes in the chemical structure of a transient mixed-disulfide intermediate adduct between a protein cysteine and an attacking low molecular-weight thiol have a dramatic effect on the protein\&$\#$39;s mechanical stability. This approach provides a general tool to rationalize the dynamics of S-thiolation and its role in modulating protein nanomechanics, offering molecular insights on how chemical reactivity regulates protein elasticity.

}, doi = {10.1038/ncomms15658}, author = {Beedle, Amy E M and Mora, Marc and Lynham, Steven and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @article {2017|2102, title = {Visualization of Biomolecular Structures: State of the Art Revisited: Visualization of Biomolecular Structures}, journal = {Computer Graphics Forum}, volume = {36}, year = {2017}, pages = {178{\textendash}204}, issn = {01677055}, doi = {10.1111/cgf.13072}, url = {http://doi.wiley.com/10.1111/cgf.13072}, author = {Kozlikova, B. and Krone, M. and Falk, M. and Lindow, N. and Marc Baaden and Baum, D. and Viola, I. and Parulek, J. and Hege, H.-C.} } @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|1415, title = {Interactive visual analytics of molecular data in immersive environments via a semantic definition of the content and the context}, booktitle = {2016 Workshop on Immersive Analytics (IA)}, year = {2016}, month = {March}, abstract = {

Bringing together, in a unique immersive environment, visualization and analysis of scientific and complex data requires a thorough approach in order to fulfill scientists\&$\#$39; specific expectations. Such an approach needs to consider the highly heterogeneous nature of data, the dynamic interactions between experts and data, and the large amount of data involved in scientific studies. Whereas small and static scientific datasets can quickly be deciphered thanks to standard immersive tools such as 3D visualization software packages, bigger and dynamic datasets exceed the analytical capacity of these tools, requiring an efficient platform for their manipulation. Through the example of the structural biology field we discuss the need for an approach based on a high-level definition of the content (scientific data) and the context (immersive environments and interfaces). Our design is illustrated by a platform for dynamic and intelligent representation of data to the user. The data hierarchical classification will provide new ways to interact with the data via intelligent and direct relationships between them. This approach is based on the semantic definition of all the concepts manipulated in the virtual environment, either abstract or concrete, which allows for an adaptive and interactive experience of both visualization and analysis.

}, keywords = {Computer Graphics [I.3.7]: Three-Dimensional Graphics and Realism-Virtual Reality, content high-level definition, content management, content semantic definition, Context, context high-level definition, context semantic definition, data analysis, data dynamic representation, data intelligent representation, data visualisation, Data visualization, molecular data interactive visual analysis, Ontologies, Resource description framework, Semantics, static scientific datasets, structural biology field, Three-dimensional displays, Tools, virtual environment, Virtual Reality}, doi = {10.1109/IMMERSIVE.2016.7932383}, author = {M. Trellet and Nicolas F{\'e}rey and Marc Baaden and P. Bourdot} } @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|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|1447, title = {{S}alt-{E}xcluding {A}rtificial {W}ater {C}hannels {E}xhibiting {E}nhanced {D}ipolar {W}ater and {P}roton {T}ranslocation}, journal = {J. Am. Chem. Soc.}, volume = {138}, number = {16}, year = {2016}, month = {apr}, pages = {5403{\textendash}5409}, author = {Licsandru, E. and Kocsis, I. and Shen, Y. X. and Murail, S. and Legrand, Y. M. and van der Lee, A. and Tsai, D. and Marc Baaden and Kumar, M. and Barboiu, M.} } @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} } @article {2016|1763, title = {Structure of ring-shaped Aβ42 oligomers determined by conformational selection}, journal = {Sci. Rep.}, volume = {6}, year = {2016}, pages = {21429}, abstract = {

The oligomerization of amyloid beta (Aβ) peptides into soluble non-fibrillar species plays a critical role in the pathogenesis of Alzheimer\&$\#$39;s disease. However, it has been challenging to characterize the tertiary and quaternary structures of Aβ peptides due to their disordered nature and high aggregation propensity. In this work, replica exchange molecular dynamics simulations were used to explore the conformational space of Aβ42 monomer. Among the most populated transient states, we identified a particular conformation which was able to generate ring-shaped pentamers and hexamers, when docked onto itself. The structures of these aggregates were stable during microsecond all-atom MD simulations in explicit solvent. In addition to high resolution models of these oligomers, this study provides support for the conformational selection mechanism of Aβ peptide self-assembly.

}, issn = {2045-2322}, doi = {10.1038/srep21429}, author = {Tran, Linh and Basdevant, Nathalie and Chantal Pr{\'e}vost and Ha-Duong, T{\^a}p} } @article {2016, title = {Visual Analysis of Biomolecular Cavities: State of the Art}, journal = {Comput. Graphics Forum}, volume = {35}, number = {3}, year = {2016}, month = {jun}, pages = {527{\textendash}551}, keywords = {AMBIENT OCCLUSION, ANALYTICAL SHAPE, BINDING-SITE IDENTIFICATION, LIGAND-BINDING, PORE DIMENSIONS, PROTEIN CAVITIES, SURFACE, TIME MOLECULAR VISUALIZATION, TRAVEL DEPTH, WEB SERVER}, url = {https://hal.archives-ouvertes.fr/hal-01400464}, author = {Krone, M. and Kozlikova, B. and Lindow, N. and Marc Baaden and Baum, D. and Parulek, J. and Hege, H.-C. and Viola, I.} } @article {2016|1401, title = {Visualization of Biomolecular Structures: State of the Art Revisited}, journal = {Comput. Graphics Forum}, year = {2016}, month = {nov}, url = {https://hal.archives-ouvertes.fr/hal-01400465}, author = {Kozlikova, B. and Krone, M. and Falk, M. and Lindow, N. and Marc Baaden and Baum, D. and Viola, I. and Parulek, J. and Hege, H.-C.} } @article {2016|1633, title = {Water Determines the Structure and Dynamics of Proteins}, journal = {Chem. Rev.}, volume = {116}, year = {2016}, pages = {7673{\textendash}7697}, author = {M-C. Bellissent-Funel and A. Hassanali and M. Havenith and R. Henchman and P. Pohl and Fabio Sterpone and D. van der Spoel and Y. Xu and A. E. Garcia} } @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|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} } @conference {2015|1556, title = {Content and task based navigation for structural biology in 3D environments}, booktitle = {Virtual and Augmented Reality for Molecular Science (VARMS@IEEEVR), 2015 IEEE 1st International Workshop on}, year = {2015}, month = {mar}, pages = {31{\textendash}36}, keywords = {3D environment, biology computing, Cameras, content navigation, data visualisation, feature extraction, molecular biology, molecule visualisation, Navigation, Pro, rendering (computer graphics), stereoscopic rendering feature, structural biology, task based navigation}, author = {M. Trellet and Nicolas F{\'e}rey and Marc Baaden and P. Bourdot} } @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|1582, title = {The elastic free energy of a tandem modular protein under force.}, journal = {Biochem. Biophys. Res. Comm.}, year = {2015}, pages = {1{\textendash}5}, keywords = {free energy landscape, tandem modular protein}, issn = {0006291X}, doi = {10.1016/j.bbrc.2015.03.051}, url = {http://linkinghub.elsevier.com/retrieve/pii/S0006291X15004866}, author = {Valle-Orero, Jessica and Eckels, Edward and Guillaume Stirnemann and Popa, Ionel and Berkovich, Ronen and Fernandez, Julio M.} } @article {2015|1755, title = {How osmolytes influence hydrophobic polymer conformations: A unified view from experiment and theory.}, journal = {Proc. Natl. Acad. Sci. Usa}, volume = {112}, year = {2015}, pages = {9270{\textendash}5}, abstract = {

It is currently the consensus belief that protective osmolytes such as trimethylamine N-oxide (TMAO) favor protein folding by being excluded from the vicinity of a protein, whereas denaturing osmolytes such as urea lead to protein unfolding by strongly binding to the surface. Despite there being consensus on how TMAO and urea affect proteins as a whole, very little is known as to their effects on the individual mechanisms responsible for protein structure formation, especially hydrophobic association. In the present study, we use single-molecule atomic force microscopy and molecular dynamics simulations to investigate the effects of TMAO and urea on the unfolding of the hydrophobic homopolymer polystyrene. Incorporated with interfacial energy measurements, our results show that TMAO and urea act on polystyrene as a protectant and a denaturant, respectively, while complying with Tanford-Wyman preferential binding theory. We provide a molecular explanation suggesting that TMAO molecules have a greater thermodynamic binding affinity with the collapsed conformation of polystyrene than with the extended conformation, while the reverse is true for urea molecules. Results presented here from both experiment and simulation are in line with earlier predictions on a model Lennard-Jones polymer while also demonstrating the distinction in the mechanism of osmolyte action between protein and hydrophobic polymer. This marks, to our knowledge, the first experimental observation of TMAO-induced hydrophobic collapse in a ternary aqueous system.

}, keywords = {Atomic Force, Computer Simulation, Hydrophobic and Hydrophilic Interactions, Mechanical, Methylamines, Methylamines: chemistry, Microscopy, Molecular Dynamics Simulation, Normal Distribution, Polymers, Polymers: chemistry, Polystyrenes, Polystyrenes: chemistry, Protein Binding, Protein Conformation, Protein Folding, Proteins, Proteins: chemistry, Software, Solvents, Solvents: chemistry, Stress, Thermodynamics, Urea, Urea: chemistry, Water, Water: chemistry}, isbn = {1215421109}, issn = {1091-6490}, doi = {10.1073/pnas.1511780112}, url = {http://www.pnas.org/content/112/30/9270}, author = {Mondal, Jagannath and Halverson, Duncan and Li, Isaac T S and Guillaume Stirnemann and Walker, Gilbert C and Berne, Bruce J} } @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|1965, title = {An integrative approach to the study of filamentous oligomeric assemblies, with application to {R}ec{A}}, journal = {Plos One}, volume = {in press}, year = {2015}, pages = {e0116414}, abstract = {

Oligomeric macromolecules in the cell self-organize into a wide variety of geometrical motifs such as helices, rings or linear filaments. The recombinase proteins involved in homologous recombination present many such assembly motifs. Here, we examine in particular the polymorphic characteristics of RecA, the most studied member of the recombinase family, using an integrative approach that relates local modes of monomer/monomer association to the global architecture of their screw-type organization. In our approach, local modes of association are sampled via docking or Monte Carlo simulations. This enables shedding new light on fiber morphologies that may be adopted by the RecA protein. Two distinct RecA helical morphologies, the so-called \"extended\" and \"compressed\" forms, are known to play a role in homologous recombination. We investigate the variability within each form in terms of helical parameters and steric accessibility. We also address possible helical discontinuities in RecA filaments due to multiple monomer-monomer association modes. By relating local interface organization to global filament morphology, the strategies developed here to study RecA self-assembly are particularly well suited to other DNA-binding proteins and to filamentous protein assemblies in general.

}, doi = {10.1371/journal.pone.0116414}, author = {Benjamin Boyer and Johann Ezelin and Pierre Poulain and A Saladin and Martin Zacharias and Charles H. Robert and Chantal Pr{\'e}vost} } @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|1729, title = {The mechanochemistry of copper reports on the directionality of unfolding in model cupredoxin proteins.}, journal = {Nature Comm.}, volume = {6}, year = {2015}, pages = {7894}, abstract = {

Understanding the directionality and sequence of protein unfolding is crucial to elucidate the underlying folding free energy landscape. An extra layer of complexity is added in metalloproteins, where a metal cofactor participates in the correct, functional fold of the protein. However, the precise mechanisms by which organometallic interactions are dynamically broken and reformed on (un)folding are largely unknown. Here we use single molecule force spectroscopy AFM combined with protein engineering and MD simulations to study the individual unfolding pathways of the blue-copper proteins azurin and plastocyanin. Using the nanomechanical properties of the native copper centre as a structurally embedded molecular reporter, we demonstrate that both proteins unfold via two independent, competing pathways. Our results provide experimental evidence of a novel kinetic partitioning scenario whereby the protein can stochastically unfold through two distinct main transition states placed at the N and C termini that dictate the direction in which unfolding occurs.

}, isbn = {doi:10.1038/ncomms8894}, issn = {2041-1723}, doi = {10.1038/ncomms8894}, url = {http://www.nature.com/ncomms/2015/150803/ncomms8894/abs/ncomms8894.html}, author = {Beedle, Amy E M and Lezamiz, Ainhoa and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @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|1549, title = {{N}othing to sneeze at: a dynamic and integrative computational model of an influenza {A} virion}, journal = {Structure}, volume = {23}, number = {3}, year = {2015}, month = {mar}, pages = {584{\textendash}597}, author = {Reddy, T. and Shorthouse, D. and Parton, D. L. and Jefferys, E. and Fowler, P. W. and Matthieu Chavent and Marc Baaden and Sansom, M. S.} } @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|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, title = {{T}aming molecular flexibility to tackle rare diseases}, journal = {Biochimie}, volume = {113}, year = {2015}, pages = {54{\textendash}58}, author = {Cubellis, M. V. and Marc Baaden and Andreotti, G.} } @article {2015|1414, title = {{T}hree-dimensional representations of complex carbohydrates and polysaccharides{\textendash}{S}weet{U}nity{M}ol: a video game-based computer graphic software}, journal = {Glycobiology}, volume = {25}, number = {5}, year = {2015}, month = {may}, pages = {483{\textendash}491}, author = {Perez, S. and Tubiana, T. and Imberty, A. and Marc Baaden} } @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|1408, title = {Visualization of Biomolecular Structures: State of the Art}, booktitle = {Eurographics Conference on Visualization (EuroVis) - STARs}, year = {2015}, publisher = {The Eurographics Association}, organization = {The Eurographics Association}, author = {Kozlikova, Barbora and Krone, Michael and Lindow, Norbert and Falk, Martin and Marc Baaden and Baum, Daniel and Viola, Ivan and Parulek, Julius and Hege, Hans-Christian}, editor = {R. Borgo and F. Ganovelli and I. Viola} } @conference {2014|1385, title = {Content-guided Navigation in Multimeric Molecular Complexes}, booktitle = {{BIOIMAGING} 2014 - Proceedings of the International Conference on Bioimaging, ESEO, Angers, Loire Valley, France, 3-6 March, 2014}, year = {2014}, pages = {76{\textendash}81}, doi = {10.5220/0004914300760081}, author = {M. Trellet and Nicolas F{\'e}rey and Marc Baaden and P. Bourdot} } @article {2014|1433, title = {{A} cooperative mechanism of clotrimazoles in {P}450 revealed by the dissociation picture of clotrimazole from {P}450}, journal = {J. Chem. Inf. Model.}, volume = {54}, number = {4}, year = {2014}, note = {[DOI:\href{http://dx.doi.org/10.1021/ci400660e}{10.1021/ci400660e}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24611729}{24611729}]}, month = {apr}, pages = {1218{\textendash}1225}, author = {Wang, M. and Marc Baaden and Wang, J. and Liang, Z.} } @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.} } @inbook {2014|1720, title = {Foundations of Biomolecular Simulations: A Critical Introduction to Homology Modeling, Molecular Dynamics Simulations, and Free Energy Calculations of Membrane Proteins}, booktitle = {Membrane Proteins Production for Structural Analysis}, year = {2014}, pages = {347{\textendash}392}, publisher = {Springer New York}, organization = {Springer New York}, author = {J{\'e}r{\^o}me H{\'e}nin and Marc Baaden and Antoine Taly} } @article {2014|1751, title = {How force unfolding differs from chemical denaturation.}, journal = {Proc. Natl. Acad. Sci. U.s.a}, volume = {111}, year = {2014}, pages = {3413{\textendash}8}, abstract = {

Single-molecule force spectroscopies are remarkable tools for studying protein folding and unfolding, but force unfolding explores protein configurations that are potentially very different from the ones traditionally explored in chemical or thermal denaturation. Understanding these differences is crucial because such configurations serve as starting points of folding studies, and thus can affect both the folding mechanism and the kinetics. Here we provide a detailed comparison of both chemically induced and force-induced unfolded state ensembles of ubiquitin based on extensive, all-atom simulations of the protein either extended by force or denatured by urea. As expected, the respective unfolded states are very different on a macromolecular scale, being fully extended under force with no contacts and partially extended in urea with many nonnative contacts. The amount of residual secondary structure also differs: A significant population of $\alpha$-helices is found in chemically denatured configurations but such helices are absent under force, except at the lowest applied force of 30 pN where short helices form transiently. We see that typical-size helices are unstable above this force, and $\beta$-sheets cannot form. More surprisingly, we observe striking differences in the backbone dihedral angle distributions for the protein unfolded under force and the one unfolded by denaturant. A simple model based on the dialanine peptide is shown to not only provide an explanation for these striking differences but also illustrates how the force dependence of the protein dihedral angle distributions give rise to the worm-like chain behavior of the chain upon force.

}, keywords = {Chemical, Hydrogen-Ion Concentration, Models, Molecular Dynamics Simulation, Protein Conformation, Protein Denaturation, Protein Folding, Protein Unfolding, Ubiquitin, Ubiquitin: chemistry, Urea, Urea: chemistry}, issn = {1091-6490}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24550471}, author = {Guillaume Stirnemann and Kang, Seung-gu and Zhou, Ruhong and Berne, Bruce J} } @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|1637, title = {{L}ong distance effect on ligand-gated ion channels extracellular domain may affect interactions with the intracellular machinery}, journal = {Commun. Integr. Biol.}, volume = {7}, year = {2014}, pages = {e27984}, author = {Garret, M. and Boue-Grabot, E. and Antoine Taly} } @article {2014|1717, title = {Lipid concentration and molar ratio boundaries for the use of isotropic bicelles.}, journal = {Langmuir}, volume = {30}, number = {21}, year = {2014}, month = {jun}, pages = {6162{\textendash}6170}, publisher = {Department of Chemistry, Universit{\'e} du Qu{\'e}bec {\`a} Montr{\'e}al and Centre Qu{\'e}b{\'e}cois sur les Mat{\'e}riaux Fonctionnels , P.O. Box 8888, Downtown Station, Montreal, Canada H3C 3P8.}, abstract = {Bicelles are model membranes generally made of long-chain dimyristoylphosphatidylcholine (DMPC) and short-chain dihexanoyl-PC (DHPC). They are extensively used in the study of membrane interactions and structure determination of membrane-associated peptides, since their composition and morphology mimic the widespread PC-rich natural eukaryotic membranes. At low DMPC/DHPC (q) molar ratios, fast-tumbling bicelles are formed in which the DMPC bilayer is stabilized by DHPC molecules in the high-curvature rim region. Experimental constraints imposed by techniques such as circular dichroism, dynamic light scattering, or microscopy may require the use of bicelles at high dilutions. Studies have shown that such conditions induce the formation of small aggregates and alter the lipid-to-detergent ratio of the bicelle assemblies. The objectives of this work were to determine the exact composition of those DMPC/DHPC isotropic bicelles and study the lipid miscibility. This was done using (31)P nuclear magnetic resonance (NMR) and exploring a wide range of lipid concentrations (2-400 mM) and q ratios (0.15-2). Our data demonstrate how dilution modifies the actual DMPC/DHPC molar ratio in the bicelles. Care must be taken for samples with a total lipid concentration <=250 mM and especially at q \~{} 1.5-2, since moderate dilutions could lead to the formation of large and slow-tumbling lipid structures that could hinder the use of solution NMR methods, circular dichroism or dynamic light scattering studies. Our results, supported by infrared spectroscopy and molecular dynamics simulations, also show that phospholipids in bicelles are largely segregated only when q > 1. Boundaries are presented within which control of the bicelles{\textquoteright} q ratio is possible. This work, thus, intends to guide the choice of q ratio and total phospholipid concentration when using isotropic bicelles.}, keywords = {chemistry, Circular Dichroism, Detergents, Dimyristoylphosphatidylcholine, Fourier Transform Infrared, Light, Lipid Bilayers, Magnetic Resonance Spectroscopy, Materials Testing, Micelles, Molecular Dynamics Simulation, Phospholipid Ethers, Phospholipids, Radiation, Scattering, Solutions, Spectroscopy, Temperature}, doi = {10.1021/la5004353}, author = {Beaugrand, Ma\"{\i}wenn and Arnold, Alexandre A. and J{\'e}r{\^o}me H{\'e}nin and Warschawski, Dror E. and Williamson, Philip T F. and Marcotte, Isabelle} } @article {2014|1413, title = {{M}olecular simulations and visualization: introduction and overview}, journal = {Faraday Discuss.}, volume = {169}, year = {2014}, note = {[DOI:\href{http://dx.doi.org/10.1039/c4fd90024c}{10.1039/c4fd90024c}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25285906}{25285906}]}, pages = {9{\textendash}22}, author = {Hirst, J. D. and Glowacki, D. R. and Marc Baaden} } @article {2014|2015, title = {Multiscale Simulations Give Insight into the Hydrogen In and Out Pathways of [NiFe]-Hydrogenases from Aquifex aeolicus and Desulfovibrio fructosovorans}, journal = {J. Phys. Chem. B}, volume = {118}, number = {48}, year = {2014}, month = {dec}, pages = {13800{\textendash}13811}, doi = {10.1021/jp5089965}, author = {Oteri, F and Marc Baaden and Lojou, E and S Sacquin-Mora} } @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|1598, title = {A predicted binding site for cholesterol on the GABAA receptor.}, journal = {Biophys. J.}, volume = {106}, number = {9}, year = {2014}, month = {may}, pages = {1938{\textendash}1949}, publisher = {Department of Physics, Rutgers University-Camden, Camden, New Jersey; Center for Computational and Integrative Biology, Rutgers University-Camden, Camden, New Jersey. Electronic address: Grace.Brannigan@rutgers.edu.}, abstract = {Modulation of the GABA type A receptor (GABAAR) function by cholesterol and other steroids is documented at the functional level, yet its structural basis is largely unknown. Current data on structurally related modulators suggest that cholesterol binds to subunit interfaces between transmembrane domains of the GABAAR. We construct homology models of a human GABAAR based on the structure of the glutamate-gated chloride channel GluCl of Caenorhabditis elegans. The models show the possibility of previously unreported disulfide bridges linking the M1 and M3 transmembrane helices in the α and γ subunits. We discuss the biological relevance of such disulfide bridges. Using our models, we investigate cholesterol binding to intersubunit cavities of the GABAAR transmembrane domain. We find that very similar binding modes are predicted independently by three approaches: analogy with ivermectin in the GluCl crystal structure, automated docking by AutoDock, and spontaneous rebinding events in unbiased molecular dynamics simulations. Taken together, the models and atomistic simulations suggest a somewhat flexible binding mode, with several possible orientations. Finally, we explore the possibility that cholesterol promotes pore opening through a wedge mechanism.}, keywords = {Amino Acid, Binding Sites, Caenorhabditis elegans Proteins, chemistry, chemistry/metabolism, Chloride Channels, Cholesterol, GABA-A, Humans, Hydrogen Bonding, Ivermectin, metabolism, Molecular Docking Simulation, Molecular Dynamics Simulation, Porosity, Protein Binding, Protein Conformation, Receptors, Sequence Homology, Substrate Specificity}, doi = {10.1016/j.bpj.2014.03.024}, author = {J{\'e}r{\^o}me H{\'e}nin and Salari, Reza and Murlidaran, Sruthi and Grace Brannigan} } @article {2014|1518, title = {{T}he weak, fluctuating, dipole moment of membrane-bound hydrogenase from {A}quifex aeolicus accounts for its adaptability to charged electrodes}, journal = {Phys. Chem. Chem. Phys.}, volume = {16}, number = {23}, year = {2014}, month = {may}, pages = {11318{\textendash}11322}, author = {Oteri, F and Ciaccafava, A and Poulpiquet, A and Marc Baaden and Lojou, E and S Sacquin-Mora} } @article {2014|1645, title = {Type VI secretion and bacteriophage tail tubes share a common assembly pathway.}, journal = {Embo Rep.}, volume = {15}, year = {2014}, month = {mar}, pages = {315{\textendash}21}, abstract = {

The Type VI secretion system (T6SS) is a widespread macromolecular structure that delivers protein effectors to both eukaryotic and prokaryotic recipient cells. The current model describes the T6SS as an inverted phage tail composed of a sheath-like structure wrapped around a tube assembled by stacked Hcp hexamers. Although recent progress has been made to understand T6SS sheath assembly and dynamics, there is no evidence that Hcp forms tubes in vivo. Here we show that Hcp interacts with TssB, a component of the T6SS sheath. Using a cysteine substitution approach, we demonstrate that Hcp hexamers assemble tubes in an ordered manner with a head-to-tail stacking that are used as a scaffold for polymerization of the TssB/C sheath-like structure. Finally, we show that VgrG but not TssB/C controls the proper assembly of the Hcp tubular structure. These results highlight the conservation in the assembly mechanisms between the T6SS and the bacteriophage tail tube/sheath.

}, keywords = {Amino Acid Sequence, Bacterial Secretion Systems, Escherichia coli, Escherichia coli Proteins, Molecular Sequence Data, Protein Binding, Protein Multimerization, Protein Structure, Tertiary, Virulence Factors}, issn = {1469-3178}, doi = {10.1002/embr.201337936}, author = {Brunet, Yannick R and J{\'e}r{\^o}me H{\'e}nin and Celia, Herv{\'e} and Cascales, Eric} } @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} } @article {2013|1699, title = {Agonist-dependent endocytosis of $\gamma$-aminobutyric acid type A (GABAA) receptors revealed by a $\gamma$2 (R43Q) epilepsy mutation}, journal = {J. Biol. Chem.}, volume = {288}, number = {39}, year = {2013}, pages = {28254{\textendash}28265}, publisher = {American Society for Biochemistry and Molecular Biology}, author = {Chaumont, Severine and Andr{\'e}, Caroline and Perrais, David and Bou{\'e}-Grabot, Eric and Antoine Taly and Garret, Maurice} } @article {2013|1403, title = {{C}oarse-grain modelling of protein-protein interactions}, journal = {Curr. Opin. Struct. Biol.}, volume = {23}, number = {6}, year = {2013}, pages = {878{\textendash}886}, author = {Marc Baaden and Marrink, S. J.} } @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|1752, title = {Elasticity, structure, and relaxation of extended proteins under force.}, journal = {Proc. Natl. Acad. Sci. U.s.a}, volume = {110}, year = {2013}, pages = {3847{\textendash}52}, abstract = {

Force spectroscopies have emerged as a powerful and unprecedented tool to study and manipulate biomolecules directly at a molecular level. Usually, protein and DNA behavior under force is described within the framework of the worm-like chain (WLC) model for polymer elasticity. Although it has been surprisingly successful for the interpretation of experimental data, especially at high forces, the WLC model lacks structural and dynamical molecular details associated with protein relaxation under force that are key to the understanding of how force affects protein flexibility and reactivity. We use molecular dynamics simulations of ubiquitin to provide a deeper understanding of protein relaxation under force. We find that the WLC model successfully describes the simulations of ubiquitin, especially at higher forces, and we show how protein flexibility and persistence length, probed in the force regime of the experiments, are related to how specific classes of backbone dihedral angles respond to applied force. Although the WLC model is an average, backbone model, we show how the protein side chains affect the persistence length. Finally, we find that the diffusion coefficient of the protein{\textquoteright}s end-to-end distance is on the order of 10(8) nm(2)/s, is position and side-chain dependent, but is independent of the length and independent of the applied force, in contrast with other descriptions.

}, keywords = {Atomic Force, Biophysical Phenomena, Computer Simulation, Elasticity, Mechanical, Microscopy, Models, Molecular, Molecular Dynamics Simulation, Proteins, Proteins: chemistry, Stress, Ubiquitin, Ubiquitin: chemistry}, issn = {1091-6490}, url = {http://www.pnas.org/content/early/2013/02/13/1300596110.abstract}, author = {Guillaume Stirnemann and Giganti, David and Fernandez, Julio M and Berne, B J} } @article {2013|1525, title = {{F}ormation of raft-like assemblies within clusters of influenza hemagglutinin observed by {M}{D} simulations}, journal = {Plos Comput. Biol.}, volume = {9}, number = {4}, year = {2013}, month = {apr}, pages = {e1003034}, author = {Parton, D. L. and Tek, A. and Marc Baaden and Sansom, M. S.} } @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|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} } @article {2013|1426, title = {MANHaptic: A Haptic Adaptive Method for Precise Manipulation, Assembly \and Navigation}, journal = {International Journal on Human Machine Interaction}, volume = {1}, year = {2013}, pages = {60{\textendash}67}, author = {A. Tek and Marc Baaden and Nicolas F{\'e}rey and P. Bourdot} } @article {2013|1747, title = {A mutation causes MuSK reduced sensitivity to agrin and congenital myasthenia}, journal = {Plos One}, volume = {8}, number = {1}, year = {2013}, publisher = {Public Library of Science}, author = {Ammar, A Ben and Soltanzadeh, Payam and Bauch{\'e}, St{\'e}phanie and Richard, Pascale and Goillot, Evelyne and Herbst, Ruth and Gaudon, Karen and Huz{\'e}, Caroline and Schaeffer, Laurent and Yamanashi, Yuji and others} } @conference {2013|1381, title = {Navigation guid{\'e}e par le contenu pour l{\textquoteright}exploration mol{\'e}culaire.}, booktitle = {Actes de l{\textquoteright}AFRV}, year = {2013}, author = {M. Trellet and Nicolas F{\'e}rey and Marc Baaden and P. Bourdot} } @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|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} } @article {2013|1430, title = {{U}nderstanding small biomolecule-biomaterial interactions: a review of fundamental theoretical and experimental approaches for biomolecule interactions with inorganic surfaces}, journal = {J. Biomed. Mater. Res. A}, volume = {101}, number = {4}, year = {2013}, month = {apr}, pages = {1210{\textendash}1222}, author = {Costa, D. and Garrain, P. A. and Marc Baaden} } @article {2013|1689, title = {When Does Trimethylamine N-Oxide Fold a Polymer Chain and Urea Unfold It?}, journal = {J. Phys. Chem. B}, volume = {117}, year = {2013}, pages = {8723{\textendash}8732}, abstract = {

Longstanding mechanistic questions about the role of protecting osmolyte trimethylamine N-oxide (TMAO) that favors protein folding and the denaturing osmolyte urea are addressed by studying their effects on the folding of uncharged polymer chains. Using atomistic molecular dynamics simulations, we show that 1 M TMAO and 7 M urea solutions act dramatically differently on these model polymer chains. Their behaviors are sensitive to the strength of the attractive dispersion interactions of the chain with its environment: when these dispersion interactions are sufficiently strong, TMAO suppresses the formation of extended conformations of the hydrophobic polymer as compared to water while urea promotes the formation of extended conformations. Similar trends are observed experimentally for real protein systems. Quite surprisingly, we find that both protecting and denaturing osmolytes strongly interact with the polymer, seemingly in contrast with existing explanations of the osmolyte effect on proteins. We show that what really matters for a protective osmolyte is its effective depletion as the polymer conformation changes, which leads to a negative change in the preferential binding coefficient. For TMAO, there is a much more favorable free energy of insertion of a single osmolyte near collapsed conformations of the polymer than near extended conformations. By contrast, urea is preferentially stabilized next to the extended conformation and thus has a denaturing effect.

}, isbn = {15206106}, url = {http://pubs.acs.org/doi/abs/10.1021/jp405609j$\backslash$nhttp://pubs.acs.org/doi/pdf/10.1021/jp405609j$\backslash$nhttp://dx.doi.org/10.1021/jp405609j}, author = {Mondal, Jagannath and Guillaume Stirnemann and Berne, B J} } @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|1382, title = {Bient{\^o}t dans votre amphith{\'e}{\^a}tre, la chimie fera son cin{\'e}ma. De la bonne utilisation des ressources informatiques pour l{\textquoteright}enseignement : visualisation mol{\'e}culaire, illustration de processus chimiques et de mod{\`e}les physiques}, journal = {Actualit{\'e} Chimique}, volume = {363}, year = {2012}, author = {Matthieu Chavent and Marc Baaden and E. H{\'e}non and S. Antonczak} } @article {2012|1554, title = {Early Stage of the Dehydrogenation of NaAlH4 by Ab Initio Rare Event Simulations}, journal = {The Journal of Physical Chemistry C}, volume = {116}, number = {37}, year = {2012}, pages = {19636{\textendash}19643}, doi = {10.1021/jp3019588}, author = {Sterpone, Fabio and Bonella, Sara and Meloni, Simone} } @article {2012|1960, title = {General Anesthetics Predicted to Block the {GLIC} Pore with Micromolar Affinity}, journal = {Plos Comput. Biol.}, volume = {8}, number = {5}, year = {2012}, pages = {e1002532}, publisher = {Public Library of Science}, abstract = {

Author Summary

Although general anesthesia is performed every day on thousands of people, its detailed microscopic mechanisms are not known. What is known is that general anesthetic drugs modulate the activity of ion channels in the central nervous system. These channels are proteins that open in response to binding of neurotransmitter molecules, creating an electric current through the cell membrane and thus propagating nerve impulses between cells. One possible mechanism for ion channel inhibition by anesthetics is that the drugs bind inside the pore of the channels, blocking ion current. Here we investigate such a pore block mechanism by computing the strength of the drugs{\textquoteright} interaction with the pore {\textendash} and hence the likelihood of binding, in the case of GLIC, a bacterial channel protein. The results, obtained from numerical simulations of atomic models of GLIC, indicate that the anesthetics isoflurane and propofol have a tendency to bind in the pore that is strong enough to explain blocking of the channel, even at low concentration of the drugs.

}, doi = {10.1371/journal.pcbi.1002532}, url = {http://dx.doi.org/10.1371\%2Fjournal.pcbi.1002532}, author = {LeBard, David N. and J{\'e}r{\^o}me H{\'e}nin and Roderic G Eckenhoff and Michael L Klein and Brannigan, Grace} } @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|1753, title = {Rate limit of protein elastic response is tether dependent}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {109}, year = {2012}, pages = {14416{\textendash}14421}, abstract = {

The elastic restoring force of tissues must be able to operate over the very wide range of loading rates experienced by living organisms. It is surprising that even the fastest events involving animal muscle tissues do not surpass a few hundred hertz. We propose that this limit is set in part by the elastic dynamics of tethered proteins extending and relaxing under a changing load. Here we study the elastic dynamics of tethered proteins using a fast force spectrometer with sub-millisecond time resolution, combined with Brownian and Molecular Dynamics simulations. We show that the act of tethering a polypeptide to an object, an inseparable part of protein elasticity in vivo and in experimental setups, greatly reduces the attempt frequency with which the protein samples its free energy. Indeed, our data shows that a tethered polypeptide can traverse its free-energy landscape with a surprisingly low effective diffusion coefficient D(eff) \~{} 1,200 nm(2)/s. By contrast, our Molecular Dynamics simulations show that diffusion of an isolated protein under force occurs at D(eff) \~{} 10(8) nm(2)/s. This discrepancy is attributed to the drag force caused by the tethering object. From the physiological time scales of tissue elasticity, we calculate that tethered elastic proteins equilibrate in vivo with D(eff) \~{} 10(4)-10(6) nm(2)/s which is two to four orders magnitude smaller than the values measured for untethered proteins in bulk.

}, issn = {0027-8424}, author = {Berkovich, R. and Hermans, R. I. and Popa, I. and Guillaume Stirnemann and Garcia-Manyes, S. and Berne, B. J. and Fernandez, J. M.} } @article {2012|1527, title = {{S}tructure-function analysis of the {NFL}-{TBS}.40-63 peptide corresponding to the binding site of tubulin on the light neurofilament subunit}, journal = {Plos One}, volume = {7}, year = {2012}, pages = {e49436}, author = {Berges, R. and Balzeau, J. and Takahashi, M. and Chantal Pr{\'e}vost and Eyer, J.} } @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 {2011|1654, title = {Accounting for large amplitude protein deformation during in silico macromolecular docking}, journal = {Int. J. Mol. Sci.}, volume = {12}, year = {2011}, pages = {1316{\textendash}33}, abstract = {

Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

}, keywords = {flexibility, macromolecular docking, protein loops and domains}, doi = {10.3390/ijms12021316}, author = {Bastard, Karine and A Saladin and Chantal Pr{\'e}vost} } @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|1653, title = {On the characterization and selection of diverse conformational ensembles with applications to flexible docking}, journal = {Ieee/acm Trans. Comput. Biol. Bioinform.}, volume = {8}, year = {2011}, pages = {487{\textendash}98}, abstract = {

To address challenging flexible docking problems, a number of docking algorithms pregenerate large collections of candidate conformers. To remove the redundancy from such ensembles, a central problem in this context is to report a selection of conformers maximizing some geometric diversity criterion. We make three contributions to this problem. First, we resort to geometric optimization so as to report selections maximizing the molecular volume or molecular surface area (MSA) of the selection. Greedy strategies are developed, together with approximation bounds. Second, to assess the efficacy of our algorithms, we investigate two conformer ensembles corresponding to a flexible loop of four protein complexes. By focusing on the MSA of the selection, we show that our strategy matches the MSA of standard selection methods, but resorting to a number of conformers between one and two orders of magnitude smaller. This observation is qualitatively explained using the Betti numbers of the union of balls of the selection. Finally, we replace the conformer selection problem in the context of multiple-copy flexible docking. On the aforementioned systems, we show that using the loops selected by our strategy can improve the result of the docking process.

}, doi = {10.1109/TCBB.2009.59}, author = {Loriot, S{\'e}bastien and Sachdeva, Sushant and Bastard, Karine and Chantal Pr{\'e}vost and Fr{\'e}d{\'e}ric Cazals} } @article {2011|1771, title = {Coherent Excitation Transfer Driven by Torsional Dynamics: a Model Hamiltonian for PPV Type Systems}, journal = {Zeitschrift F{\"u}r Physikalische Chemie}, volume = {255}, year = {2011}, pages = {541{\textendash}551}, author = {Fabio Sterpone and R. Martinazzo and A.N. Panda and I. Burghardt} } @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|1857, title = {{D}iscrimination of agonists versus antagonists of nicotinic ligands based on docking onto {A}{C}h{B}{P} structures}, journal = {J. Mol. Graph. Model.}, volume = {30}, year = {2011}, month = {sep}, pages = {100{\textendash}109}, author = {Antoine Taly and Colas, C. and Malliavin, T. and Blondel, A. and Nilges, M. and Corringer, P. J. and Joseph, D.} } @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|1446, title = {{F}rontier residues lining globin internal cavities present specific mechanical properties}, journal = {J. Am. Chem. Soc.}, volume = {133}, year = {2011}, month = {jun}, pages = {8753{\textendash}8761}, author = {Bocahut, A. and Bernad, S. and Sebban, P. and S Sacquin-Mora} } @article {2011|1848, title = {Free energy profiles along consensus normal modes provide insight into {HIV}-1 protease flap opening}, journal = {J. Chem. Theor. Comput.}, volume = {7}, year = {2011}, pages = {2348{\textendash}52}, author = {Paulo R. Batista and Gaurav Pandey and Paulo M. Bisch and Paulo G. Pascutti and David Perahia and Charles H. Robert} } @conference {2011, title = {FvNano: A Virtual Laboratory to Manipulate Molecular Systems}, booktitle = {1st IEEE symposium on biological data visualization, Providence, RI @ ieee visweek, 2011, N$\#$ 136}, year = {2011}, url = {http://www.biovis.net/materials/abstracts/BioVispaper136.pdf}, author = {Matthieu Chavent and Marc Piuzzi and Alex Tek and Marc Baaden} } @article {2011|1437, title = {GPU-accelerated atom and dynamic bond visualization using HyperBalls: a unified algorithm for balls, sticks and hyperboloids}, journal = {J. Comput. Chem.}, volume = {32}, number = {13}, year = {2011}, month = {oct}, pages = {2924{\textendash}2935}, doi = {10.1002/jcc.21861/abstract}, author = {Matthieu Chavent and A. Vanel and A. Tek and B. L{\'e}vy and S. Robert and B. Raffin and Marc Baaden} } @article {2011|1393, title = {GPU-powered tools boost molecular visualization}, journal = {Briefings Bioinf.}, volume = {12}, year = {2011}, month = {feb}, pages = {689{\textendash}701}, author = {Matthieu Chavent and B. L{\'e}vy and M. Krone and K. Bidmon and J. P. Nomin{\'e} and T. Ertl and Marc Baaden} } @article {2011|1739, title = {Water reorientation dynamics in the first hydration shells of F- and I-}, journal = {Phys. Chem. Chem. Phys.}, volume = {13}, year = {2011}, pages = {19895}, abstract = {

Molecular dynamics and analytic theory results are presented for the reorientation dynamics of first hydration shell water molecules around fluoride and iodide anions. These ions represent the extremes of the (normal) halide series in terms of their size and conventional structure-making and -breaking categorizations. The simulated reorientation times are consistent with NMR and ultrafast IR experimental results. They are also in good agreement with the theoretical predictions of the analytic Extended Jump Model. Analysis through this model shows that while sudden, large amplitude jumps (in which the reorienting water exchanges hydrogen-bond partners) are the dominant reorientation pathway for the I(-) case, they are comparatively less important for the F(-) case. In particular, the diffusive reorientation of an intact F(-)...H(2)O hydrogen-bonded pair is found to be most important for the reorientation time, a feature related to the greater hydrogen-bond strength for the F(-)...H(2)O pair. The dominance of this effect for e.g. multiply charged ions is suggested.

}, issn = {1463-9076}, author = {Boisson, Jean and Guillaume Stirnemann and Laage, Damien and Hynes, James T.} } @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|1749, title = {A computational study of a recreated {G} protein-{GEF} reaction intermediate competent for nucleotide exchange: fate of the {M}g ion}, journal = {Plos One}, volume = {5}, number = {2}, year = {2010}, month = {feb}, pages = {e9142}, publisher = {Public Library of Science}, abstract = {

Small G-proteins of the superfamily Ras function as molecular switches, interacting with different cellular partners according to their activation state. G-protein activation involves the dissociation of bound GDP and its replacement by GTP, in an exchange reaction that is accelerated and regulated in the cell by guanine-nucleotide exchange factors (GEFs). Large conformational changes accompany the exchange reaction, and our understanding of the mechanism is correspondingly incomplete. However, much knowledge has been derived from structural studies of blocked or inactive mutant GEFs, which presumably closely represent intermediates in the exchange reaction and yet which are by design incompetent for carrying out the nucleotide exchange reaction. In this study we have used comparative modelling to recreate an exchange-competent form of a late, pre-GDP-ejection intermediate species in Arf1, a well-characterized small G-protein. We extensively characterized three distinct models of this intermediate using molecular dynamics simulations, allowing us to address ambiguities related to the mutant structural studies. We observed in particular the unfavorable nature of Mg2+ associated forms of the complex and the establishment of closer Arf1-GEF contacts in its absence. The results of this study shed light on GEF-mediated activation of this small G protein and on predicting the fate of the Mg ion at a critical point in the exchange reaction. The structural models themselves furnish additional targets for interfacial inhibitor design, a promising direction for exploring potentially druggable targets with high biological specificity.

}, doi = {10.1371/journal.pone.0009142}, url = {http://dx.doi.org/10.1371\%2Fjournal.pone.0009142}, author = {M{\'e}riam Ben Hamida{\textendash}Reba\"{\i} and Charles H. Robert} } @article {2010|1736, title = {Consensus {M}odes, a robust description of protein collective motions from multiple-minima normal mode analysis{\textendash}application to the {HIV}-1 protease.}, journal = {Phys. Chem. Chem. Phys.}, volume = {12}, year = {2010}, month = {mar}, pages = {2850{\textendash}2859}, abstract = {

Protein flexibility is essential for enzymatic function, ligand binding, and protein-protein or protein-nucleic acid interactions. Normal mode analysis has increasingly been shown to be well suited for studying such flexibility, as it can be used to identify favorable structural deformations that correspond to functional motions. However, normal modes are strictly relevant to a single structure, reflecting a particular minimum on a complex energy surface, and are thus susceptible to artifacts. We describe a new theoretical framework for determining \"consensus\" normal modes from a set of related structures, such as those issuing from a short molecular dynamics simulation. This approach is more robust than standard normal mode analysis, and provides higher collectivity and symmetry properties. In an application to HIV-1 protease, the low-frequency consensus modes describe biologically relevant motions including flap opening and closing that can be used in interpreting structural changes accompanying the binding of widely differing inhibitors.

}, doi = {10.1039/b919148h}, author = {Paulo R. Batista and Charles H. Robert and Jean-Didier Mar{\'e}chal and M{\'e}riam Ben Hamida{\textendash}Reba\"{\i} and Paulo Pascutti and Paulo M. Bisch and David P. Perahia} } @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|1524, title = {{H}ow cations can assist {D}{N}ase {I} in {D}{N}{A} binding and hydrolysis}, journal = {Plos Comput. Biol.}, volume = {6}, year = {2010}, month = {nov}, pages = {e1001000}, author = {M. Gueroult and D. Picot and J. Abi-Ghanem and B. Hartmann and Marc Baaden} } @article {2010|1788, title = {How does heparin prevent the p{H} inactivation of cathepsin {B}? Allosteric mechanism elucidated by docking and molecular dynamics.}, journal = {Bmc Genomics}, volume = {11, S5}, year = {2010}, author = {Mauricio G.S. Costa and Paulo R. Batista and Cl{\`a}udio S Shida and Charles H. Robert and Paulo M. Bisch and Pedro G. Pascutti} } @conference {2010|1410, title = {Interacting with Molecular Simulations using a Multimodal VR Framework}, booktitle = {EuroVR-EVE}, year = {2010}, pages = {1{\textendash}4}, address = {Orsay, France}, author = {A Tek and B Laurent and Nicolas F{\'e}rey and Marc Baaden} } @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} } @inbook {2010|1569, title = {Molecular dynamics studies of outer membrane proteins : a story of barrels}, year = {2010}, pages = {225{\textendash}247}, publisher = {Royal Society of Chemistry}, organization = {Royal Society of Chemistry}, chapter = {Molecular Simulations and Biomembranes: From Biophysics to Function}, address = {United Kingdom}, author = {S. Khalid and Marc Baaden}, editor = {P.C. Biggin and M.S.P. Sansom} } @article {2010|1971, title = {Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain.}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {107}, number = {32}, year = {2010}, pages = {14122{\textendash}14127}, abstract = {An extensive search for isoflurane binding sites in the nicotinic acetylcholine receptor (nAChR) and the proton gated ion channel from Gloebacter violaceus (GLIC) has been carried out based on molecular dynamics (MD) simulations in fully hydrated lipid membrane environments. Isoflurane introduced into the aqueous phase readily partitions into the lipid membrane and the membrane-bound protein. Specifically, isoflurane binds persistently to three classes of sites in the nAChR transmembrane domain: (i) An isoflurane dimer occludes the pore, contacting residues identified by previous mutagenesis studies; analogous behavior is observed in GLIC. (ii) Several nAChR subunit interfaces are also occupied, in a site suggested by photoaffinity labeling and thought to positively modulate the receptor; these sites are not occupied in GLIC. (iii) Isoflurane binds to the subunit centers of both nAChR alpha chains and one of the GLIC chains, in a site that has had little experimental targeting. Interpreted in the context of existing structural and physiological data, the present MD results support a multisite model for the mechanism of receptor-channel modulation by anesthetics.}, doi = {10.1073/pnas.1008534107}, author = {Grace Brannigan and David N LeBard and J{\'e}r{\^o}me H{\'e}nin and Roderic G Eckenhoff and Michael L Klein} } @article {2010|1685, title = {Non adiabatic simulations of exciton dissociation in poly-p-phenylenevinylene oligomers}, journal = {J. Phys. Chem. A}, volume = {114}, year = {2010}, pages = {7661{\textendash}7670}, author = {M. Bedard-Hearn and Fabio Sterpone and P.J. Rossky} } @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.} } @conference {2010|1459, title = {A Rendering Method for Small Molecules up to Macromolecular Systems: HyperBalls Accelerated by Graphics Processors}, booktitle = {JOBIM}, year = {2010}, author = {Matthieu Chavent and A. Vanel and B. L{\'e}vy and B. Raffin and A. Tek and Marc Baaden} } @mastersthesis {2010|1570, title = {Simulations num{\'e}riques de syst{\`e}mes biologiques complexes : dynamique, structure et fonction de transporteurs, canaux et enzymes}, year = {2010}, school = {Universit{\'e} Paris-Diderot - Paris VII (15/06/2010), Fr{\'e}d{\'e}ric Dardel (Pr.)}, type = {phd}, author = {Marc Baaden} } @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 {2010|1445, title = {Water around thermophilic proteins: the role of charged and apolar atoms}, journal = {J Phys: Cond Matt}, volume = {22}, number = {28}, year = {2010}, pages = {284113}, author = {Fabio Sterpone and Claudia Bertonati and Giuseppe Briganti and Simone Melchionna} } @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|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|1509, title = {{E}ts-1 p51 and p42 isoforms differentially modulate {S}tromelysin-1 promoter according to induced {D}{N}{A} bend orientation}, journal = {Nucleic Acids Res.}, volume = {37}, year = {2009}, month = {jul}, pages = {4341{\textendash}4352}, author = {Leprivier, G. and Baillat, D. and Begue, A. and Hartmann, B. and Aumercier, M.} } @article {2009|1605, title = {The HSP90 binding mode of a radicicol-like E-oxime determined by docking, binding free energy estimations, and NMR 15 N chemical shifts}, journal = {Biophys. Chem.}, volume = {143}, number = {3}, year = {2009}, pages = {111{\textendash}123}, publisher = {Elsevier}, author = {Spichty, Martin and Antoine Taly and Hagn, Franz and Kessler, Horst and Barluenga, Sofia and Winssinger, Nicolas and Karplus, Martin} } @article {2009|1831, title = {Key role of proximal water in regulating thermostable proteins}, journal = {J. Phys. Chem. B}, volume = {113}, number = {1}, year = {2009}, month = {jan}, pages = {131{\textendash}7}, abstract = {Three homologous proteins with mesophilic, thermophilic and hyperthermophilic character have been studied via molecular dynamics simulations at four different temperatures in order to investigate how water controls thermostability. The water-exposed surface of the protein is shown to increase with the degree of thermophilicity, and the role of water in enhancing the protein internal flexibility and structural robustness is elucidated. The presence of water-water hydrogen bond clusters enveloping the macromolecule is shown to correlate with thermal robustness when going from the mesophilic to the hyperthermophilic variants. Our analysis indicates that essential contributions to thermostability stem from protein-water surface effects whereas the protein internal packing plays a minor role.}, doi = {10.1021/jp805199c}, author = {Sterpone, Fabio and Bertonati, Claudia and Briganti, Giuseppe and Melchionna, Simone} } @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|1440, title = {Nonadiabatic mixed quantum-classical dynamic simulation of pi-stacked oligophenylenevinylenes}, journal = {J. Phys. Chem. A}, volume = {113}, number = {15}, year = {2009}, pages = {3427{\textendash}30}, author = {Sterpone, Fabio and Bedard-Hearn, Michael J and Rossky, Peter J} } @article {2009|1443, title = {{R}elating the {D}iffusion of {S}mall {L}igands in {H}uman {N}euroglobin to {I}ts {S}tructural and {M}echanical {P}roperties}, journal = {J. Phys. Chem. B}, volume = {113}, number = {50}, year = {2009}, month = {nov}, pages = {16257{\textendash}16267}, author = {Bocahut, A. and Bernad, S. and Sebban, P. and S Sacquin-Mora} } @article {2009|1495, title = {Sphere versus cylinder: the effect of packing on the structure of nonionic C12E6 micelles}, journal = {Langmuir}, volume = {25}, number = {16}, year = {2009}, pages = {8960{\textendash}7}, author = {Sterpone, Fabio and Briganti, G and Pierleoni, C} } @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|1808, title = {Anomalous diffusion of ions at the surface of hydrated DNA molecule}, journal = {Europhys. Lett.}, volume = {82}, year = {2008}, pages = {46002}, author = {Alla Oleinikova and Ivan Brovchenko and Aliaksei Krukau and Alexey K Mazur} } @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|1970, title = {Embedded cholesterol in the nicotinic acetylcholine receptor}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {105}, number = {38}, year = {2008}, pages = {14418{\textendash}14423}, publisher = {Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA. grace@cmm.upenn.edu}, abstract = {The nicotinic acetylcholine receptor (nAChR) is a cation-selective channel central to both neuronal and muscular processes and is considered the prototype for ligand-gated ion channels, motivating a structural determination effort that spanned several decades [Unwin N (2005) Refined structure of the nicotinic acetylcholine receptor at 4 A resolution. J Mol Biol 346:967-989]. Purified nAChR must be reconstituted in a mixture containing cholesterol to function. Proposed modes of interaction between cholesterol and the protein range from specific binding to indirect membrane-mediated mechanisms. However, the underlying cause of nAChR sensitivity to cholesterol remains controversial, in part because the vast majority of functional studies were conducted before a medium resolution structure was reported. We show that the nAChR contains internal sites capable of containing cholesterol, whose occupation stabilizes the protein structure. We detect sites at the protein-lipid interface as conventionally predicted from functional data, as well as deeply buried sites that are not usually considered. Molecular dynamics simulations reveal that occupation of both superficial and deeply buried sites most effectively preserves the experimental structure; the structure collapses in the absence of bound cholesterol. In particular, we find that bound cholesterol directly supports contacts between the agonist-binding domain and the pore that are thought to be essential for activation of the receptor. These results likely apply to those other ion channels within the Cys-loop superfamily that depend on cholesterol, such as the GABA receptor.}, doi = {10.1073/pnas.0803029105}, author = {Grace Brannigan and J{\'e}r{\^o}me H{\'e}nin and Richard Law and Roderic G Eckenhoff and Michael L Klein} } @article {2008|1485, title = {Energy transport in peptide helices: A comparison between high- and low-energy excitations}, journal = {J. Phys. Chem. B}, volume = {112}, number = {30}, year = {2008}, month = {jul}, pages = {9091{\textendash}9099}, author = {Backus, Ellen H. G. and Phuong Hoang Nguyen and Botan, Virgiliu and Pfister, Rolf and Moretto, Alessandro and Crisma, Marco and Toniolo, Claudio and Stock, Gerhard and Hamm, Peter} } @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|1940, title = {HU binds and folds single-stranded DNA}, journal = {Nucl. Acids Res.}, volume = {36}, number = {3}, year = {2008}, pages = {1026{\textendash}1036}, author = {Dmitri Kamashev and Anna Balandina and Alexey K Mazur and Paola B. Arimondo and Josette Rouviere-Yaniv} } @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|1840, title = {Ion dynamics and water percolation effects in DNA polymorphism}, journal = {J. Am. Chem. Soc.}, volume = {130}, number = {1}, year = {2008}, pages = {121{\textendash}131}, author = {Ivan Brovchenko and Aliaksei Krukau and Alla Oleinikova and Alexey K Mazur} } @article {2008|1390, title = {Microseconds dynamics simulations of the outer-membrane protease T}, journal = {Biophys. J.}, volume = {94}, number = {1}, year = {2008}, month = {jan}, pages = {71{\textendash}78}, author = {Neri, Marilisa and Marc Baaden and Carnevale, Vincenzo and Anselmi, Claudio and Maritan, Amos and Carloni, Paolo} } @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} } @article {2008|1409, title = {Outer membrane proteins: comparing X-ray and NMR structures by MD simulations in lipid bilayers}, journal = {European Biophysics Journal with Biophysics Letters}, volume = {37}, number = {2}, year = {2008}, month = {feb}, pages = {131{\textendash}141}, author = {Cox, Katherine and Bond, Peter J. and Grottesi, Alessandro and Marc Baaden and Sansom, Mark S. P.} } @article {2008|1494, title = {Pressure-induced core packing and interfacial dehydration in nonionic C12E6 micelle in aqueous solution}, journal = {Langmuir}, volume = {24}, number = {12}, year = {2008}, pages = {6067{\textendash}71}, author = {Sterpone, Fabio and Briganti, G and Melchionna, S and Pierleoni, C} } @article {2008|1484, title = {Structural Flexibility of a Helical Peptide Regulates Vibrational Energy Transport Properties}, journal = {J. Phys. Chem. B}, volume = {112}, number = {48}, year = {2008}, month = {dec}, pages = {15487{\textendash}15492}, author = {Backus, Ellen H. G. and Phuong Hoang Nguyen and Botan, Virgiliu and Moretto, Alessandro and Crisma, Marco and Toniolo, Claudio and Zerbe, Oliver and Stock, Gerhard and Hamm, Peter} } @conference {2008|1552, title = {User Needs Analysis to Design a 3D Multimodal Protein-Docking Interface}, booktitle = {Symposium on 3D User Interfaces 2008 (3DUI 2008 - IEEE)}, year = {2008}, month = {mar}, pages = {125{\textendash}132}, publisher = {Reno - USA}, organization = {Reno - USA}, author = {Nicolas F{\'e}rey and G. Bouyer and C. Martin and P. Bourdot and J. Nelson and and J.M. Burkhardt} } @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|1534, title = {Energy transport in peptide helices}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {104}, number = {31}, year = {2007}, month = {jul}, pages = {12749{\textendash}12754}, author = {Botan, Virgiliu and Backus, Ellen H. G. and Pfister, Rolf and Moretto, Alessandro and Crisma, Marco and Toniolo, Claudio and Phuong Hoang Nguyen and Stock, Gerhard and Hamm, Peter} } @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|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|1547, title = {{T}he 1.3 {A} resolution structure of the {R}{N}{A} tridecamer r({G}{C}{G}{U}{U}{U}{G}{A}{A}{A}{C}{G}{C}): metal ion binding correlates with base unstacking and groove contraction}, journal = {Rna}, volume = {13}, year = {2007}, month = {dec}, pages = {2098{\textendash}2107}, author = {Y Timsit and Bombard, S.} } @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 {2007|1477, title = {Three hydrolases and a transferase: Comparative analysis of active-site dynamics via the BioSimGrid database}, journal = {Journal of Molecular Graphics \& Modelling}, volume = {25}, number = {6}, year = {2007}, month = {mar}, pages = {896{\textendash}902}, author = {Tai, Kaihsu and Marc Baaden and Murdock, Stuart and Wu, Bing and Ng, Muan Hong and Johnston, Steven and Boardman, Richard and Fangohr, Hans and Cox, Katherine and Essex, Jonathan W. and Sansom, Mark S. P.} } @article {2007|1861, title = {Water clustering and percolation in low hydration DNA shells}, journal = {J. Phys. Chem. B}, volume = {111}, number = {12}, year = {2007}, pages = {3258{\textendash}3266}, author = {Ivan Brovchenko and Aliaksei Krukau and Alla Oleinikova and Alexey K Mazur} } @article {2006|1536, title = {Accounting for loop flexibility during protein-protein docking}, journal = {Proteins}, volume = {62}, number = {4}, year = {2006}, month = {mar}, pages = {956{\textendash}969}, author = {Bastard, K and Chantal Pr{\'e}vost and Martin Zacharias} } @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|1843, title = {Comparison of different torsion angle approaches for NMR structure determination}, journal = {J. Biol. Nmr}, volume = {34}, number = {3}, year = {2006}, pages = {153{\textendash}166}, author = {B. Bardiaux and T. E. Malliavin and M. Nilges and Alexey K Mazur} } @article {2006|1935, title = {HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription.}, journal = {Mol. Cell}, volume = {22}, number = {5}, year = {2006}, month = {jun}, pages = {669{\textendash}679}, publisher = {Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Building 41, B602, Bethesda, Maryland 20892, USA.}, abstract = {Although histone deacetylases (HDACs) are generally viewed as corepressors, we show that HDAC1 serves as a coactivator for the glucocorticoid receptor (GR). Furthermore, a subfraction of cellular HDAC1 is acetylated after association with the GR, and this acetylation event correlates with a decrease in promoter activity. HDAC1 in repressed chromatin is highly acetylated, while the deacetylase found on transcriptionally active chromatin manifests a low level of acetylation. Acetylation of purified HDAC1 inactivates its deacetylase activity, and mutation of the critical acetylation sites abrogates HDAC1 function in vivo. We propose that hormone activation of the receptor leads to progressive acetylation of HDAC1 in vivo, which in turn inhibits the deacetylase activity of the enzyme and prevents a deacetylation event that is required for promoter activation. These findings indicate that HDAC1 is required for the induction of some genes by the GR, and this activator function is dynamically modulated by acetylation.}, keywords = {Acetylation, Amino Acid Sequence, Animals, Binding Sites, Cell Cycle Proteins, Chromatin, Down-Regulation, genetics/metabolism, Hela Cells, Histone Acetyltransferases, Histone Deacetylases, Humans, immunology/metabolism, metabolism}, doi = {10.1016/j.molcel.2006.04.019}, author = {Yi Qiu and Yingming Zhao and Matthias Becker and Sam John and Bhavin S Parekh and Suming Huang and Anindya Hendarwanto and Elisabeth D Martinez and Yue Chen and Hanxin Lu and Nicholas L Adkins and Diana A Stavreva and Malgorzata Wiench and Philippe T Geor} } @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} } @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|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|1827, title = {Structure and dynamics of hydrogen bonds in the interface of a C12E6 spherical micelle in water solution: a MD study at various temperatures}, journal = {J. Phys. Chem. B}, volume = {110}, number = {37}, year = {2006}, pages = {18254{\textendash}61}, author = {Sterpone, Fabio and Pierleoni, Carlo and Briganti, Giuseppe and Marchi, Massimo} } @article {2006|1948, title = {Water percolation governs polymorphic transitions and conductivity of DNA}, journal = {Phys. Rev. Lett.}, volume = {97}, number = {13}, year = {2006}, pages = {137801}, author = {Ivan Brovchenko and Aliaksei Krukau and Alla Oleinikova and Alexey K Mazur} } @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|1476, title = {Membrane protein structure quality in molecular dynamics simulation}, journal = {Journal of Molecular Graphics \& Modelling}, volume = {24}, number = {2}, year = {2005}, note = {International Meeting of the Molecular-Graphics-and-Modelling-Society, Manchester, ENGLAND, 2004}, month = {oct}, pages = {157{\textendash}165}, author = {Law, RJ and Capener, C and Marc Baaden and Bond, PJ and Campbell, J and Patargias, G and Arinaminpathy, Y and Sansom, MSP} } @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|1801, title = {Molecular cloning of a mollusk glucanase}, journal = {Comp. Biochem. Physiol.}, volume = {137}, number = {2}, year = {2004}, pages = {169{\textendash}178}, author = {Valeri B. Kozhemyako and Denis V. Rebrikov and Sergey A. Lukyanov and Ekaterina A. Bogdanova and Antoine Marin and Alexey K Mazur and Svetlana N. Kovalchuk and Elena V. Agafonova and Victoria V. Sova and Ludmila A. Elyakova and Valeri A. Rasskazov} } @article {2004|1493, title = {Molecular dynamics study of temperature dehydration of a C12E6 spherical micelle}, journal = {Langmuir}, volume = {20}, number = {11}, year = {2004}, pages = {4311{\textendash}4}, author = {Sterpone, Fabio and Pierleoni, Carlo and Briganti, Giuseppe and Marchit, Massimo} } @article {2004|1826, title = {Molecular Modeling and Simulations of AOT{\^a}{\textasciicircum}{\textquoteright}Water Reverse Micelles in Isooctane:{\^a}{\texteuro}{\textperthousand} Structural and Dynamic Properties}, journal = {J. Phys. Chem. B}, volume = {108}, number = {50}, year = {2004}, pages = {19458{\textendash}19466}, author = {Abel, St{\'e}phane and Sterpone, Fabio and Bandyopadhyay, Sanjoy and Marchi, Massimo} } @article {2004, title = {OmpT: Molecular dynamics simulations of an outer membrane enzyme}, journal = {Biophys. J.}, volume = {87}, number = {5}, year = {2004}, month = {nov}, pages = {2942{\textendash}2953}, author = {Marc Baaden and Sansom, MSP} } @article {2004|1718, title = {Temperature dehydration of C12E6 micelle}, journal = {Langmuir}, volume = {20}, year = {2004}, pages = {4311{\textendash}4314}, author = {Fabio Sterpone and C. Pierleoni and G. Briganti and M. Marchi} } @article {2003|1663, title = {Docking macromolecules with flexible segments}, journal = {J. Comput. Chem.}, volume = {24}, year = {2003}, month = {nov}, pages = {1910{\textendash}20}, abstract = {

We address a major obstacle to macromolecular docking algorithms by presenting a new method that takes into account the induced conformational adjustment of flexible loops situated at a protein/macromolecule interface. The method, MC2, is based on a multiple copy representation of the loops, coupled with a Monte Carlo conformational search of the relative position of the macromolecules and their side chain conformations. The selection of optimal loop conformations takes place during Monte Carlo cycling by the iterative adjustment of the weight of each copy. We describe here the parameterization of the method and trials on a protein-DNA complex of known 3-D structure, involving the Drosophila prd paired domain protein and its target oligonucleotide Wenqing, X. et al., Cell 1995, 80, 639. We demonstrate that our algorithm can correctly configure and position this protein, despite its relatively complex interactions with both grooves of DNA.

}, doi = {10.1002/jcc.10329}, author = {Bastard, Karine and Thureau, Aur{\'e}lien and Richard Lavery and Chantal Pr{\'e}vost} } @article {2003, title = {Extending the structure of an ABC transporter to atomic resolution: Modeling and simulation studies of MsbA}, journal = {Biochemistry}, volume = {42}, number = {13}, year = {2003}, month = {apr}, pages = {3666{\textendash}3673}, author = {Campbell, JD and Biggin, PC and Marc Baaden and Sansom, MSP} } @article {2003|1475, title = {A molecular dynamics investigation of mono and dimeric states of the outer membrane enzyme OMPLA}, journal = {J. Mol. Biol.}, volume = {331}, number = {1}, year = {2003}, month = {aug}, pages = {177{\textendash}189}, author = {Marc Baaden and Meier, C and Sansom, MSP} } @article {2003|1548, title = {Theoretical studies on lanthanide cation extraction by picolinamides: Ligand-cation interactions and interfacial behavior}, journal = {Solvent Extr. Ion Exch.}, volume = {21}, number = {2}, year = {2003}, pages = {199{\textendash}220}, author = {Marc Baaden and Berny, F and Madic, C and Schurhammer, R and Wipff, G} } @conference {2002|1622, title = {Cd2+ binding effect on bacterial reaction center mutants: The proton penetration involves interdependent pathways}, booktitle = {BIOPHYSICAL JOURNAL}, volume = {82}, number = {1}, year = {2002}, pages = {518A-518A}, publisher = {BIOPHYSICAL SOCIETY 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA}, organization = {BIOPHYSICAL SOCIETY 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA}, author = {Gerencser, L and Antoine Taly and Baciou, L and Maroti, P and Sebban, P} } @article {2002|2002, title = {{E}ffect of binding of {C}d2+ on bacterial reaction center mutants: proton-transfer uses interdependent pathways}, journal = {Biochemistry}, volume = {41}, number = {29}, year = {2002}, month = {jul}, pages = {9132{\textendash}9138}, publisher = {ACS Publications}, author = {Gerencser, L. and Antoine Taly and Baciou, L. and Maroti, P. and Sebban, P.} } @article {2002|1483, title = {Molecular dynamics study of the uranyl extraction by tri-n-butylphosphate (TBP): Demixing of water/{{\textquoteright}{\textquoteright}}oil{{\textquoteright}{\textquoteright}}/TBP solutions with a comparison of supercritical CO2 and chloroform}, journal = {J. Phys. Chem. B}, volume = {106}, number = {2}, year = {2002}, month = {jan}, pages = {434{\textendash}441}, author = {Marc Baaden and Schurhammer, R and Wipff, G} } @article {2002|1650, title = {{T}he {D}{M}{P}{C} lipid phase transition influences differently the first and the second electron transfer reactions in bacterial reaction centers}, journal = {Febs Lett.}, volume = {532}, number = {1-2}, year = {2002}, month = {dec}, pages = {91{\textendash}96}, author = {Antoine Taly and Baciou, L. and Sebban, P.} } @article {2001|1479, title = {The chloroform TBP aqueous nitric acid interfacial system: a molecular dynamics investigation}, journal = {J. Mol. Liq.}, volume = {90}, number = {1-3, Sp. Iss. SI}, year = {2001}, note = {26th International Conference on Solution Chemistry (26 ICSC), FUKUOKA, JAPAN, JUL 26-31, 1999}, month = {feb}, pages = {1{\textendash}9}, author = {Marc Baaden and Berny, F and Wipff, G} } @inbook {2001|1640, title = {Internal coordinate simulation method}, booktitle = {Computational Biochemistry and Biophysics}, year = {2001}, pages = {115{\textendash}131}, publisher = {Marcel Dekker}, organization = {Marcel Dekker}, address = {New York}, author = {Alexey K Mazur}, editor = {Oren M. Becker and Alexander D. MacKerell and Benoit Roux and Masakatsu Watanabe} } @article {2001|1520, title = {Lanthanide cation binding to a phosphoryl-calix{[}4]arene: the importance of solvent and counterions investigated by molecular dynamics and quantum mechanical simulations}, journal = {Phys. Chem. Chem. Phys.}, volume = {3}, number = {7}, year = {2001}, pages = {1317{\textendash}1325}, author = {Marc Baaden and Burgard, M and Boehme, C and Wipff, G} } @article {2001|1933, title = {Molecular Dynamics Study of Spherical Aggregates of Chain Molecules at Different Degrees of Hydrophilicity in Water Solution}, journal = {Langmuir}, volume = {17}, number = {16}, year = {2001}, pages = {5103{\textendash}5110}, author = {Sterpone, Fabio and Briganti, Giuseppe and Pierleoni, Carlo} } @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 {2001|1482, title = {TBP at the water-oil interface: The effect of TBP concentration and water acidity investigated by molecular dynamics simulations}, journal = {J. Phys. Chem. B}, volume = {105}, number = {45}, year = {2001}, month = {nov}, pages = {11131{\textendash}11141}, author = {Marc Baaden and Burgard, M and Wipff, G} } @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|1490, title = {Cation coordination by calix{[}4]arenes bearing amide and/or phosphine oxide pendant groups: how many arms are needed to bind Li+ vs. Na+? A combined NMR and molecular dynamics study}, journal = {Journal of the Chemical Society-perkin Transactions 2}, number = {7}, year = {2000}, pages = {1315{\textendash}1321}, author = {Marc Baaden and Wipff, G and Yaftian, MR and Burgard, M and Matt, D} } @article {2000|1551, title = {Complexation of M3+ lanthanide cations by calix{[}4]arene-CMPO ligands: A molecular dynamics study in methanol solution and at a water/chloroform interface}, journal = {Supramol. Chem.}, volume = {12}, number = {1, Sp. Iss. SI}, year = {2000}, note = {International Symposium on Supramolecular Chemistry, FUKUOKA, JAPAN, 1997}, pages = {27+}, author = {Troxler, L and Marc Baaden and Bohmer, V and Wipff, G} } @article {2000|1501, title = {Dependence of NMR isotropic shift averages and nuclear shielding tensors on the internal rotation of the functional group X about the C-X bond in seven simple vinylic derivatives H2C=CH-X}, journal = {Mol. Phys.}, volume = {98}, number = {6}, year = {2000}, month = {mar}, pages = {329{\textendash}342}, author = {Marc Baaden and Granger, P and Strich, A} } @mastersthesis {2000|1560, title = {Etudes de mol{\'e}cules extractantes en solution et aux interfaces liquide-liquide: aspects structuraux et m{\'e}canistiques des effets de synergie}, year = {2000}, note = {(N�: 3630), 2 vol., 218/42 pages.}, school = {Universit{\'e} Louis Pasteur, Strasbourg}, type = {phd}, author = {Marc Baaden} } @article {2000|1460, title = {Interaction of trivalent lanthanide cations with phosphoryl derivatives, amide, anisole, pyridine and triazine ligands: a quantum mechanics study}, journal = {J. Alloys Compd.}, volume = {303}, year = {2000}, note = {22nd Rare Earth Research Conference, ARGONNE, ILLINOIS, JUL 11-15, 1999}, month = {may}, pages = {104{\textendash}111}, author = {Marc Baaden and Berny, F and Boehme, C and Muzet, N and Schurhammer, R and Wipff, G} } @inbook {2000|1559, title = {Interfacial features of assisted liquid-liquid extraction of uranyl and cesium salts: a molecular dynamics investigation}, booktitle = {ACS Symposium Series 757}, year = {2000}, pages = {71{\textendash}85}, publisher = {Oxford University Press, New York}, organization = {Oxford University Press, New York}, chapter = {Calixarenes for separations}, author = {Marc Baaden and F. Berny and N. Muzet and L. Troxler and G. Wipff}, editor = {G. Lumetta, R.D. Rogers, and A.S. Gopalan} } @article {2000|1481, title = {M3+ lanthanide cation solvation by acetonitrile: The role of cation size, counterions, and polarization effects investigated by molecular dynamics and quantum mechanical simulations}, journal = {J. Phys. Chem. A}, volume = {104}, number = {32}, year = {2000}, month = {aug}, pages = {7659{\textendash}7671}, author = {Marc Baaden and Berny, F and Madic, C and Wipff, G} } @article {2000|1431, title = {A mechanism for RecA-promoted sequence homology recognition and strand exchange between single-stranded DNA and duplex DNA, via triple-helical intermediates}, journal = {J. Biomol. Struct. Dyn.}, number = {Sp. Iss. S1}, year = {2000}, note = {11th Conversation in Biomolecular Stereodynamics, ALBANY, NEW YORK, JUN 15-19, 1999}, pages = {147{\textendash}153}, author = {Bertucat, G and Lavery, R and Chantal Pr{\'e}vost} } @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|1600, title = {A molecular model for RecA-promoted strand exchange via parallel triple-stranded helices}, journal = {Biophys. J.}, volume = {77}, year = {1999}, month = {sep}, pages = {1562{\textendash}76}, abstract = {

A number of studies have concluded that strand exchange between a RecA-complexed DNA single strand and a homologous DNA duplex occurs via a single-strand invasion of the minor groove of the duplex. Using molecular modeling, we have previously demonstrated the possibility of forming a parallel triple helix in which the single strand interacts with the intact duplex in the minor groove, via novel base interactions (Bertucat et al., J. Biomol. Struct. Dynam. 16:535-546). This triplex is stabilized by the stretching and unwinding imposed by RecA. In the present study, we show that the bases within this triplex are appropriately placed to undergo strand exchange. Strand exchange is found to be exothermic and to result in a triple helix in which the new single strand occupies the major groove. This structure, which can be equated to so-called R-form DNA, can be further stabilized by compression and rewinding. We are consequently able to propose a detailed, atomic-scale model of RecA-promoted strand exchange. This model, which is supported by a variety of experimental data, suggests that the role of RecA is principally to prepare the single strand for its future interactions, to guide a minor groove attack on duplex DNA, and to stabilize the resulting, stretched triplex, which intrinsically favors strand exchange. We also discuss how this mechanism can incorporate homologous recognition.

}, doi = {10.1016/S0006-3495(99)77004-9}, author = {Bertucat, G and Richard Lavery and Chantal Pr{\'e}vost} } @booklet {1999|1558, title = {Molecular Modeling with the ChemOffice Ultra 4.5 program suite.}, year = {1999}, author = {Marc Baaden} } @article {1998|1530, title = {Folding and Aggregation of Designed Protein Chains}, journal = {Proc. Natl. Acad. Sci. Usa}, volume = {95}, year = {1998}, pages = {12930{\textendash}1293}, author = {R.A. Broglia and G. Tiana and S. Pasquali and H. E. Roman and E. Vigezzi} } @article {1998|1659, title = {A model for parallel triple helix formation by RecA: single-single association with a homologous duplex via the minor groove}, journal = {J. Biomol. Struct. Dyn.}, volume = {16}, year = {1998}, month = {dec}, pages = {535{\textendash}46}, abstract = {

The nucleoproteic filaments of RecA polymerized on single stranded DNA are able to integrate double stranded DNA in a coaxial arrangement (with DNA stretched by a factor 1.5), to recognize homologous sequences in the duplex and to perform strand exchange between the single stranded and double stranded molecules. While experimental results favor the hypothesis of an invasion of the minor groove of the duplex by the single strand, parallel minor groove triple helices have never been isolated or even modeled, the minor groove offering little space for a third strand to interact. Based on an internal coordinate modeling study, we show here that such a structure is perfectly conceivable when the two interacting oligomers are stretched by a factor 1.5, in order to open the minor groove of the duplex. The model helix presents characteristics that coincide with known experimental data on unwinding, base pair inclination and inter-proton distances. Moreover, we show that extension and unwinding stabilize the triple helix. New patterns of triplet interaction via the minor groove are presented.

}, doi = {10.1080/07391102.1998.10508268}, author = {Bertucat, G and Richard Lavery and Chantal Pr{\'e}vost} } @article {1997|1680, title = {Collective-variable Monte Carlo simulation of DNA}, journal = {J. Comp. Chem.}, volume = {18}, year = {1997}, pages = {2001{\textendash}2011}, author = {H. Gabb and Chantal Pr{\'e}vost and G. Bertucat and Charles H. Robert and Richard Lavery} } @article {1997|1819, title = {Distortions of the DNA double helix induced by 1,3-trans-diamminedichloroplatinum(II)-intrastrand cross-link: An internal coordinate molecular modeling study}, journal = {J. Biomol. Struct. Dyn.}, volume = {14}, number = {6}, year = {1997}, month = {jun}, pages = {703{\textendash}714}, abstract = {

A trans-diamminedichloroplatinum(II) (trans-DDP) intrastrand adduct within the sequence d(TCTG*TG*TC).d(GACACAGA) (where G* represents a platinated guanine) is modeled on the basis of qualitative experimental data concerning global unwinding and curvature as well as information on base pairing. Modeling is performed using the internal coordinate JUMNA program, specific to nucleic acids, and modified to include the possibility of covalently bound ligands. Calibration of the energy functions representing the Pt-N7 bond with guanine is described. The platinum atom and the platinum-nitrogen bonds are parameterized for use in the H{\"u}ckel Del Re method to calculate monopoles at each atom. These monopoles are consistent with the Flex force field included in Jumna. By developing an appropriate minimization protocol we are able to generate stable, distorted three-dimensional structures compatible with the experimental data and including an unusually high global unwinding. No a priori geometric assumptions are made in generating these structures.

}, doi = {10.1080/07391102.1997.10508173}, author = {Chantal Pr{\'e}vost and Boudvillain, M and Beudaert, P and Leng, M and Lavery, R and Vovelle, F} } @article {1995|1941, title = {Solution structure of oligonucleotides covalently linked to a psoralen derivative.}, journal = {Nucleic Acids Res.}, volume = {23}, number = {5}, year = {1995}, month = {mar}, pages = {788{\textendash}795}, abstract = {

Psoralen (pso) was attached via its C-5 position to the 5\&$\#$39;-phosphate group of an oligodeoxynucleotide d(TAAGCCG) by a hexamethylene linker (m6). Complex formation between pso-m6-d(TAAGCCG) and the complementary strands d(CGGCTTA)[7-7mer] or d(CGGCTTAT)[7-8mer] was investigated by nuclear magnetic resonance in aqueous solution. Structural informations derived from DQF-COSY and NOESY maps, revealed that the mini double helix adopts a B-form conformation and that the deoxyriboses preferentially adopt a C2\&$\#$39;-endo conformation. The nOe connectivities observed between the protons of the bases or the sugars in each duplex, and the protons of the psoralen and the hexamethylene chain, led us to propose a model involving an equilibrium between two conformations due to different locations of the psoralen. Upon UV-irradiation, the psoralen moiety cross-linked the two DNA strands at the level of 5\&$\#$39;TpA3\&$\#$39; sequences. NMR studies of the single major photo-cross-linked duplex pso-m6-d(TAAGCCG) and d(CGGCTTA) were performed. The stereochemistry of the diadduct is indeed cis-syn at both cyclobutane rings. In addition, the effects of this diadduct on the helical structure are analyzed in detail.

}, keywords = {Base Sequence, chemistry, chemistry/radiation effects, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Psoralens, Solutions}, author = {O. Bornet and Chantal Pr{\'e}vost and F. Vovelle and M. Chassignol and N. T. Thuong and G. Lancelot} } @article {1994|1968, title = {Three-dimensional structure of extended chromatin fibers as revealed by tapping-mode scanning force microscopy}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {91}, number = {24}, year = {1994}, month = {nov}, pages = {11621{\textendash}11625}, abstract = {Unfixed chicken erythrocyte chromatin fibers in very low salt have been imaged with a scanning force microscope operating in the tapping mode in air at ambient humidity. These images reveal a three-dimensional organization of the fibers. The planar "zig-zag" conformation is rare, and extended "beads-on-a-string" fibers are seen only in chromatin depleted of histones H1 and H5. Glutaraldehyde fixation reveals very similar structures. Fibers fixed in 10 mM salt appear somewhat more compacted. These results, when compared with modeling studies, suggest that chromatin fibers may exist as irregular three-dimensional arrays of nucleosomes even at low ionic strength.}, keywords = {Animals, Atomic Force, Biological, Chickens, Chromatin, Fixatives, Histones, Microscopy, Models, Non-P.H.S., Non-U.S. Gov{\textquoteright}t, Osmolar Concentration, P.H.S., Research Support, Sodium Chloride, U.S. Gov{\textquoteright}t}, author = {S. H. Leuba and G. Yang and C. Robert and B. Samori and K. van Holde and J. Zlatanova and C. Bustamante} } @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 {1993|1628, title = {Persistence analysis of the static and dynamical helix deformations of DNA oligonucleotides: application to the crystal structure and molecular dynamics simulation of d(CGCGAATTCGCG)2}, journal = {Biopolymers}, volume = {33}, year = {1993}, month = {mar}, pages = {335{\textendash}50}, abstract = {

A theory and graphical presentation for the analysis of helix structure and deformations in oligonucleotides is presented. The parameters \"persistence\" and \"flexibility\" as defined in the configurational statistics of polymers of infinite length are reformulated at the oligonucleotide level in an extension of J. A. Schellman\&$\#$39;s method [(1974) Biopolymers, Vol. 17, pp. 217-226], and used as a basis for a systematic \"Persistence Analysis\" of the helix deformation properties for all possible subsequences in the structure. The basis for the analysis is a set of link vectors referenced to individual base pairs, and is limited to sequences exhibiting only perturbed rod-like behavior, i.e., below the threshold for supercoiling. The present application of the method is concerned with a physical model for the angular component of bending, so the link vectors are defined as the unit components of a global helix axis obtained by the procedure \"Curves\" of R. Lavery and H. Sklenar [(1988) J. Biomol. Struct. Dynam., Vol. 6, pp. 63-91; (1989) ibid., Vol. 6, pp. 655-667]. A discussion of the relationship between global bending and relative orientation of base pairs is provided. Our approach is illustrated by analysis of some model oligonucleotide structures with intrinsic kinks, the crystal structure of the dodecamer d(CGCGAATTCGCG)2, and the results of two molecular dynamics simulations on this dodecamer using two variations of the GROMOS force field. The results indicate that essentially all aspects of curvature in short oligonucleotides can be determined, such as the position and orientation of each bend, the sharpness or smoothness, and the location and linearity of subsequences. In the case of molecular dynamics simulations, where a Boltzmann ensemble of structures is analyzed, the spatial extent of the deformations (flexibility) is also considered.

}, doi = {10.1002/bip.360330303}, author = {Chantal Pr{\'e}vost and Louise-May, S and Ravishanker, G and Richard Lavery and Beveridge, D L} } @article {1992|1594, title = {Multiple attack in the mechanism of endoglucanase action}, journal = {Bioorg. Chem.}, volume = {18}, year = {1992}, pages = {1141{\textendash}1163}, author = {P. V. Bezukladnikov and L. A. Elyakova and Alexey K Mazur} } @article {1991|1767, title = {Mechanism of the rearrangement of the bicyclo [4.2. 0] octan system to the bicyclo [3.2. 1] octan system}, journal = {Tetrahedron}, volume = {47}, year = {1991}, pages = {229{\textendash}238}, abstract = {

A concerted mechanism has been demonstrated for the rearrangement of a tetracyclic ion including a bicyclo [4.2.0] octan system to hibaol, using a selective deuteration on the migrating bond. The stereochemistry of the selectively introduced deuterium was determined by three routes: 1. comparison of the high field 1H NMR spectra of the deuterated and undeuterated compounds, using double irradiation; 2. high field 1H NMR, coupled with molecular mechanics calculations; 3. two dimensional homo and heteronuclear NMR.

}, doi = {10.1016/S0040-4020(01)80919-4}, url = {http://www.sciencedirect.com/science/article/pii/S0040402001809194}, author = {Bastard, Josette and Do Khac, Duc and Fetizon, Marcel and Chantal Pr{\'e}vost and Beloeil, Jean-Claude} } @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 {1989|1821, title = {Binding of oxygen and carbon monoxide to the hemocyanin from the spiny lobster}, journal = {J. Mol. Biol.}, volume = {207}, number = {4}, year = {1989}, month = {jun}, pages = {829{\textendash}832}, author = {Connelly, P R and Johnson, C R and Robert, C H and Bak, H J and Gill, S J} } @article {1987|1818, title = {Calorimetric studies of oxygen and carbon monoxide binding to human hemoglobin. Sequential binding heats for oxygen}, journal = {J. Biol. Chem.}, volume = {262}, number = {23}, year = {1987}, month = {aug}, pages = {10994{\textendash}10999}, author = {Parody-Morreale, A and Robert, C H and Bishop, G A and Gill, S J} } @article {1987|1991, title = {Gas-solution microcalorimeter for determining heat binding curves}, journal = {Rev. Sci. Instr.}, volume = {58}, year = {1987}, pages = {632{\textendash}638}, author = {Bishop, G. A. and Parody-Morreale, A. and Robert, C. and and Gill, S. 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|1781, title = {Analysis of zeros of binding polynomials for tetrameric hemoglobins}, journal = {Biophys. Chem.}, volume = {24}, number = {3}, year = {1986}, month = {aug}, pages = {295{\textendash}309}, author = {Connelly, P R and Charles H. Robert and Briggs, W E and Gill, S J} } @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} } @article {1986|1652, title = {Ion-Molecule reaction in the gas phase part VI Regioselective SN2 reaction from terpenoid diastereoisomeric diols using CI/NH 4+}, journal = {Helv. Chim. Acta}, volume = {69}, year = {1986}, pages = {806{\textendash}815}, abstract = {

A stereospecific and regioselective SN2 mechanism (Walden inversion) is observed during studies involving modified terpenoid epimeric diols in a high-pressure ion source using ammonia as a reagent gas.

}, doi = {10.1002/hlca.19860690408}, author = {Tabet, Jean-Claude and Chantal Pr{\'e}vost and Bouillot, Anne and Bastard, Josette and Manh, Due Do Khae and Tondeur, Yves} }