@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 {2022|2150, title = {Modeling the Dynamics of Protein-Protein Interfaces, How and Why?}, journal = {Molecules}, volume = {27}, year = {2022}, pages = {1841}, abstract = {

Protein-protein assemblies act as a key component in numerous cellular processes. Their accurate modeling at the atomic level remains a challenge for structural biology. To address this challenge, several docking and a handful of deep learning methodologies focus on modeling protein-protein interfaces. Although the outcome of these methods has been assessed using static reference structures, more and more data point to the fact that the interaction stability and specificity is encoded in the dynamics of these interfaces. Therefore, this dynamics information must be taken into account when modeling and assessing protein interactions at the atomistic scale. Expanding on this, our review initially focuses on the recent computational strategies aiming at investigating protein-protein interfaces in a dynamic fashion using enhanced sampling, multi-scale modeling, and experimental data integration. Then, we discuss how interface dynamics report on the function of protein assemblies in globular complexes, in fuzzy complexes containing intrinsically disordered proteins, as well as in active complexes, where chemical reactions take place across the protein-protein interface.

}, issn = {1420-3049}, doi = {10.3390/molecules27061841}, url = {https://www.mdpi.com/1420-3049/27/6/1841}, author = {Karaca, Ezgi and Pr{\'e}vost, Chantal and S Sacquin-Mora} } @article {2022|2153, title = {Multiscale Computational Study of the Conformation of the Full-Length Intrinsically Disordered Protein MeCP2.}, journal = {J Chem Inf Model}, volume = {62}, year = {2022}, month = {2022 02 28}, pages = {958-970}, abstract = {

The malfunction of the methyl-CpG binding protein 2 (MeCP2) is associated with the Rett syndrome, one of the most common causes of cognitive impairment in females. MeCP2 is an intrinsically disordered protein (IDP), making its experimental characterization a challenge. There is currently no structure available for the full-length MeCP2 in any of the databases, and only the structure of its MBD domain has been solved. We used this structure to build a full-length model of MeCP2 by completing the rest of the protein via ab initio modeling. Using a combination of all-atom and coarse-grained simulations, we characterized its structure and dynamics as well as the conformational space sampled by the ID and transcriptional repression domain (TRD) domains in the absence of the rest of the protein. The present work is the first computational study of the full-length protein. Two main conformations were sampled in the coarse-grained simulations: a globular structure similar to the one observed in the all-atom force field and a two-globule conformation. Our all-atom model is in good agreement with the available experimental data, predicting amino acid W104 to be buried, amino acids R111 and R133 to be solvent-accessible, and having a 4.1\% α-helix content, compared to the 4\% found experimentally. Finally, we compared the model predicted by AlphaFold to our Modeller model. The model was not stable in water and underwent further folding. Together, these simulations provide a detailed (if perhaps incomplete) conformational ensemble of the full-length MeCP2, which is compatible with experimental data and can be the basis of further studies, e.g., on mutants of the protein or its interactions with its biological partners.

}, issn = {1549-960X}, doi = {10.1021/acs.jcim.1c01354}, author = {Ch{\'a}vez-Garc{\'\i}a, Cecilia and J{\'e}r{\^o}me H{\'e}nin and Karttunen, Mikko} } @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 {2021, title = {Moving pictures: Reassessing docking experiments with a dynamic view of protein interfaces.}, journal = {Proteins}, year = {2021}, month = {2021 May 26}, abstract = {

The modeling of protein assemblies at the atomic level remains a central issue in structural biology, as protein interactions play a key role in numerous cellular processes. This problem is traditionally addressed using docking tools, where the quality of the models is based on their similarity to a single reference experimental structure. However, using a static reference does not take into account the dynamic quality of the protein interface. Here, we used all-atom classical Molecular Dynamics simulations to investigate the stability of the reference interface for three complexes that previously served as targets in the CAPRI competition. For each one of these targets, we also ran MD simulations for ten models that are distributed over the High, Medium and Acceptable accuracy categories. To assess the quality of these models from a dynamic perspective, we set up new criteria which take into account the stability of the reference experimental protein interface. We show that, when the protein interfaces are allowed to evolve along time, the original ranking based on the static CAPRI criteria no longer holds as over 50\% of the docking models undergo a category change (which can be either toward a better or a lower accuracy group) when reassessing their quality using dynamic information.

}, issn = {1097-0134}, doi = {10.1002/prot.26152}, author = {Chantal Pr{\'e}vost and S Sacquin-Mora} } @article {2019|2118, title = {Mesoscale biosimulations within a unified framework: from proteins to plasmids}, year = {2019}, pages = {1-12}, author = {P. Maiocchi and Philippe Derreumaux and F. Sterpone and S. Melchionna} } @article {2019|2122, title = {Modelling lipid systems in fluid with Lattice Boltzmann Molecular Dynamics simulations and hydrodynamics}, journal = {Scientific Reports}, volume = {9}, year = {2019}, pages = {16450}, abstract = {

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

}, isbn = {2045-2322}, doi = {10.1038/s41598-019-52760-y}, url = {https://doi.org/10.1038/s41598-019-52760-y}, author = {F. Brandner, Astrid and Timr, Stepan and Melchionna, Simone and Philippe Derreumaux and Marc Baaden and Sterpone, Fabio} } @article {2019|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|2120, title = {Multiscale Aggregation of the Amyloid Aβ16{\textendash}22 Peptide: From Disordered Coagulation and Lateral Branching to Amorphous Prefibrils}, journal = {The Journal of Physical Chemistry Letters}, volume = {10}, year = {2019}, pages = {1594-1599}, doi = {10.1021/acs.jpclett.9b00423}, url = {https://doi.org/10.1021/acs.jpclett.9b00423}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Sterpone, Fabio} } @article {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|2047, title = {Mechanical variations in proteins with large-scale motions highlight the formation of structural locks}, journal = {Journal of Structural Biology}, year = {2018}, keywords = {Coarse-grain simulations, Elastic network model, Protein domain motion, Proteins mechanics}, issn = {1047-8477}, doi = {https://doi.org/10.1016/j.jsb.2018.05.006}, url = {http://www.sciencedirect.com/science/article/pii/S1047847718301308}, author = {S Sacquin-Mora} } @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|2035, title = {Molecular Mechanism of Protein Unfolding under Shear: A Lattice Boltzmann Molecular Dynamics Study.}, journal = {J Phys Chem B}, volume = {122}, year = {2018}, month = {2018 Feb 08}, pages = {1573-1579}, abstract = {

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

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b10796}, author = {Sterpone, Fabio and Philippe Derreumaux and Melchionna, Simone} } @article {2018|2111, title = {Molecular mechanism of the cell membrane pore formation induced by bubble stable cavitation}, journal = {The Journal of Physical Chemistry B}, volume = {123}, year = {2018}, pages = {71{\textendash}78}, author = {Man, Viet Hoang and Truong, Phan Minh and Li, Mai Suan and Wang, Junmei and Van-Oanh, Nguyen-Thi and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2017|2023, title = {Mechanics of Protein Adaptation to High Temperatures}, journal = {J Phys Chem Lett}, volume = {8}, year = {2017}, month = {Dec}, pages = {5884-5890}, abstract = {

Inspired by Somero\&$\#$39;s corresponding state principle that relates protein enhanced thermal stability with mechanical rigidity, we deployed state of the art computational techniques (based on atomistic steered molecular dynamics and Hamiltonian-replica exchange simulations) to study the in silico realization of mechanical and thermal unfolding of two homologous Csp proteins that have evolved to thrive in different thermal environments. By complementing recent single-molecule experiments, we unambiguously show that, for these homologues whose structures are very similar, the increased thermal resistance of the thermophilic variant is not associated with an increased mechanical stability. Our approach provides microscopic insights that are otherwise inaccessible to experimental techniques, and explains why the protein weak spots for thermal and mechanical denaturation are distinct.

}, doi = {10.1021/acs.jpclett.7b02611}, author = {Guillaume Stirnemann and Sterpone, Fabio} } @article {2017|2021, title = {A membrane-inserted structural model of the yeast mitofusin Fzo1}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Aug 31}, pages = {10217}, type = {Research Article}, abstract = {

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

}, issn = {2045-2322}, doi = {10.1038/s41598-017-10687-2}, author = {De Vecchis, Dario and Cavellini, Laetitia and Marc Baaden and J{\'e}r{\^o}me H{\'e}nin and Cohen, Micka{\"e}l M and Antoine Taly} } @article {2017, title = {Mobility and core-protein binding patterns of disordered C-terminal tails in β-tubulin isotypes.}, journal = {Biochemistry}, volume = { 56}, year = {2017}, pages = {1746{\textendash}1756}, chapter = {1746}, abstract = {

Although they play a significant part in the regulation of microtubule structure, dynamics and function, the disordered C-terminal tails of tubulin remain invisible to experimental structural methods and do not appear in the crystallographic structures that are currently available in the Protein Data Bank. Interestingly, these tails concentrate most of the sequence variability between tubulin isotypes, and are the sites of the principal post-translational modifications undergone by this protein. Using homology modeling, we developed two complete models for the human αI/βI and αI/βIII tubulin isotypes that include their C-terminal tails. We then investigated the conformational variability of the two β-tails using long time-scale classical Molecular Dynamics (MD) simulations that revealed similar features, notably the unexpected presence of common anchoring regions on the surface of the tubulin dimer, but also distinctive mobility or interaction patterns, some of which could be related to the tail lengths and charge distributions. We also observed in our simulations that the C-terminal tail from the βI isotype, but not the βIII, formed contacts in the putative binding site of a recently discovered peptide that disrupts microtubule formation in glioma cells. Hindering the binding site in the βI isotype would be consistent with this peptide\’s preferential disruption of microtubule formation in glioma, whose cells overexpress βIII, compared to normal glial cells. While these observations need to be confirmed with more intensive sampling, our study opens up new perspectives for the development of isotype-specific chemotherapy drugs.

}, doi = {10.1021/acs.biochem.6b00988}, author = {Laurin, Yoann and Eyer, Joel and Charles H. Robert and Chantal Pr{\'e}vost and S Sacquin-Mora} } @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|2037, title = {Multifunctional energy landscape for a DNA G-quadruplex: An evolved molecular switch.}, journal = {J Chem Phys}, volume = {147}, year = {2017}, month = {2017 Oct 21}, pages = {152715}, abstract = {

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

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

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

}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2017.08.165}, author = {Sterpone, Fabio and Doutreligne, S{\'e}bastien and Tran, Thanh Thuy and Melchionna, Simone and Marc Baaden and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2016|1639, title = {MP2 and DFT studies of beta-D-neocarrabiose and beta-D-neocarrabiose monohydrate}, journal = {Comput. Theor. Chem.}, volume = {1091}, year = {2016}, month = {sep}, pages = {24{\textendash}30}, abstract = {MP2 and density functional theory calculations have been carried out on beta-D-neocarrabiose and its mono hydrate in order to determine the conformational preferences of these molecules in the gas phase and in solvent. Relaxed iso-energetic maps were first obtained using B3LYP/6-31G(d). Then, the lower energy conformers were further fully optimized using B3LYP, B3PW91 and MP2 methods. Overall, it was demonstrated that a lower energy conformer corresponding to the couple of dihedral angles (Phi,Psi)= (69 degrees,-117 degrees) is detected either in the gas phase or in solvent provided that full optimizations are performed on the conformers corresponding to the minima detected from the iso-energetic maps. (C) 2016 Elsevier B.V. All rights reserved.}, issn = {2210-271X}, doi = {10.1016/j.comptc.2016.07.009}, author = {Bestaoui-Berrekhchi-Berrahma, N. and Sekkal-Rahal, M. and Philippe Derreumaux and Yousfi, N.} } @article {2016|1735, title = {Multiscale simulation of molecular processes in cellular environments}, journal = {Philosophical Transactions of the Royal Society A-mathematical Physical and Engineering Sciences}, volume = {374}, number = {2080}, year = {2016}, abstract = {We describe the recent advances in studying biological systems via multiscale simulations. Our scheme is based on a coarse-grained representation of the macromolecules and a mesoscopic description of the solvent. The dual technique handles particles, the aqueous solvent and their mutual exchange of forces resulting in a stable and accurate methodology allowing biosystems of unprecedented size to be simulated. This article is part of the themed issue {\textquoteleft}Multiscale modelling at the physics-chemistry-biology interface{\textquoteright}.}, issn = {1364-503X}, doi = {10.1098/rsta.2016.0225}, author = {Chiricotto, Mara and Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {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 {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|1937, title = {Motions and mechanics: investigating conformational transitions in multi-domain proteins with coarse-grain simulations}, journal = {Mol. Simul.}, volume = {40}, number = {1-3}, year = {2014}, month = {jan}, pages = {229{\textendash}236}, doi = {10.1080/08927022.2013.843176}, author = {S Sacquin-Mora} } @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 {2013|1998, title = {{M}oving through the gate in {A}{T}{P}-activated {P}2{X} receptors}, journal = {Trends Biochem. Sci.}, volume = {38}, number = {1}, year = {2013}, month = {jan}, pages = {20{\textendash}29}, author = {Jiang, R. and Antoine Taly and Grutter, T.} } @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|1670, title = {Mechanisms of acceleration and retardation of water dynamics by ions}, journal = {J. Am. Chem. Soc.}, volume = {135}, year = {2013}, pages = {11824{\textendash}11831}, abstract = {

There are fundamental and not yet fully resolved questions concerning the impact of solutes, ions in particular, on the structure and dynamics of water, which can be formulated as follows: Are the effects of ions local or long-ranged? Is the action of cations and anions on water cooperative or not? Here, we investigate how the reorientation and hydrogen-bond dynamics of water are affected by ions in dilute and concentrated aqueous salt solutions. By combining simulations and analytic modeling, we first show that ions have a short-ranged influence on the reorientation of individual water molecules and that depending on their interaction strength with water, they may accelerate or slow down water dynamics. A simple additive picture combining the effects of the cations and anions is found to provide a good description in dilute solutions. In concentrated solutions, we show that the average water reorientation time ceases to scale linearly with salt concentration due to overlapping hydration shells and structural rearrangements which reduce the translational displacements induced by hydrogen-bond switches and increase the solution viscosity. This effect is not ion-specific and explains why all concentrated salt solutions slow down water dynamics. Our picture, which is demonstrated to be robust vis-a-vis a change in the force-field, reconciles the seemingly contradictory experimental results obtained by ultrafast infrared and NMR spectroscopies, and suggests that there are no long-ranged cooperative ion effects on the dynamics of individual water molecules in dilute solutions.

}, issn = {00027863}, author = {Guillaume Stirnemann and Wernersson, Erik and Jungwirth, Pavel and Laage, Damien} } @inbook {2013|1499, title = {Modeling macromolecular complexes: a journey across scales}, booktitle = {Modeling in Computational Biology and Biomedicine: A Multidisciplinary Endeavor}, year = {2013}, note = {(in press)}, publisher = {Springer-Verlag Berlin Heidelberg}, organization = {Springer-Verlag Berlin Heidelberg}, author = {Fr{\'e}d{\'e}ric Cazals and Tom Dreyfus and Charles H. Robert} } @article {2013|1925, title = {Molecular Mechanism of the Inhibition of EGCG on the Alzheimer A beta(1-42) Dimer}, journal = {J. Phys. Chem. B}, volume = {117}, number = {15}, year = {2013}, month = {apr}, pages = {3993{\textendash}4002}, doi = {10.1021/jp312573y}, author = {Zhang, Tong and Zhang, Jian and Philippe Derreumaux and Mu, Yuguang} } @article {2013|1770, title = {Moving through the gate in ATP-activated P2X receptors}, journal = {Trends Biochem. Sci.}, volume = {38}, number = {1}, year = {2013}, pages = {20{\textendash}29}, publisher = {Elsevier Current Trends}, author = {Jiang, Ruotian and Antoine Taly and Grutter, Thomas} } @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} } @article {2012|1488, title = {Magnitude and molecular origin of water slowdown next to a protein}, journal = {J. Am. Chem. Soc.}, volume = {134}, year = {2012}, pages = {4116{\textendash}4119}, abstract = {

Hydration shell dynamics plays a critical role in protein folding and biochemical activity and has thus been actively studied through a broad range of techniques. While all observations concur with a slowdown of water dynamics relative to the bulk, the magnitude and molecular origin of this retardation remain unclear. Via numerical simulations and theoretical modeling, we establish a molecular description of protein hydration dynamics and identify the key protein features that govern it. Through detailed microscopic mapping of the water reorientation and hydrogen-bond (HB) dynamics around lysozyme, we first determine that 80\% of the hydration layer waters experience a moderate slowdown factor of \~{}2-3, while the slower residual population is distributed along a power-law tail, in quantitative agreement with recent NMR results. We then establish that the water reorientation mechanism at the protein interface is dominated by large angular jumps similar to the bulk situation. A theoretical extended jump model is shown to provide the first rigorous determination of the two key contributions to the observed slowdown: a topological excluded-volume factor resulting from the local protein geometry, which governs the dynamics of the fastest 80\% of the waters, and a free energetic factor arising from the water-protein HB strength, which is especially important for the remaining waters in confined sites at the protein interface. These simple local factors are shown to provide a nearly quantitative description of the hydration shell dynamics.

}, issn = {00027863}, author = {Fabio Sterpone and Guillaume Stirnemann and Laage, Damien} } @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 {2011|1962, title = {A Multiscale Approach to Characterize the Early Aggregation Steps of the Amyloid-Forming Peptide GNNQQNY from the Yeast Prion Sup-35}, journal = {Plos Comput. Biol.}, volume = {7}, number = {5}, year = {2011}, month = {may}, pages = {e1002051}, doi = {10.1371/journal.pcbi.1002051}, author = {Nasica-Labouze, Jessica and Meli, Massimiliano and Philippe Derreumaux and Colombo, Giorgio and Mousseau, Normand} } @article {2011|1587, title = {Mycoplasma gallisepticum produces a histone-like protein that recognizes base mismatches in DNA}, journal = {Biochemistry}, volume = {50}, year = {2011}, pages = {8692{\textendash}8702}, author = {Dmitri Kamashev and Jacques Oberto and Marina Serebryakova and Alexey Gorbachev and Yulia Zhukova and Sergei Levitskii and Alexey K Mazur and Vadim Govorun} } @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 {2009|1799, title = {{M}odeling the {M}echanical {R}esponse of {P}roteins to {A}nisotropic {D}eformation}, journal = {Chemphyschem}, volume = {10}, number = {1}, year = {2009}, month = {jan}, pages = {115{\textendash}118}, doi = {10.1002/cphc.200800480}, author = {S Sacquin-Mora and Lavery, R.} } @article {2009|1500, title = {Mean field and the confined single homopolymer}, journal = {Mol. Phys.}, volume = {107}, number = {13}, year = {2009}, pages = {1303{\textendash}1312}, author = {S. Pasquali and J. K. Percus} } @article {2009|1850, title = {Modeling DNA dynamics under steady deforming forces and torques}, journal = {J. Chem. Theory Comput.}, volume = {5}, year = {2009}, pages = {2149{\textendash}2157}, author = {Alexey K Mazur} } @article {2009|1864, title = {Models for phosphatidylglycerol lipids put to a structural test}, journal = {J. Phys. Chem. B}, volume = {113}, number = {19}, year = {2009}, pages = {6958{\textendash}6963}, publisher = {Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA. jhenin@cmm.chem.upenn.edu}, abstract = {Three atomistic empirical models for phosphatidylglycerol (PG) lipids are tested against structural data in the crystal and liquid crystal states. Simulations of the anhydrous crystal of dimyristoyl-phosphatidylglycerol (DMPG) show that only the CHARMM force field describes the conformation and interactions of PG head groups accurately. The other two models do not reproduce the native network of hydrogen bonds, suggesting the presence of biases in their conformational and nonbonded interaction properties. The CHARMM model is further validated in the biologically relevant liquid crystal phase by comparing experimental small-angle X-ray scattering spectra from DMPG unilamellar vesicles with data calculated from fluid bilayer simulations. The good agreement found in this model-free comparison implies that liquid crystal PG bilayers as described by CHARMM exhibit realistic bilayer thickness and lateral packing. Last, this model is used to simulate a fluid bilayer of palmitoyl-oleoyl-phosphatidylglycerol (POPG). The resulting view of the POPG bilayer structure is at variance with that proposed previously based on simulations, in particular, with respect to lateral packing of head groups and the role of counterions.}, keywords = {chemistry, Crystallography, Lipid Bilayers, Models, Molecular, Phosphatidylglycerols, Scattering, Small Angle, Water, X-Ray}, doi = {10.1021/jp900645z}, author = {J{\'e}r{\^o}me H{\'e}nin and Wataru Shinoda and Michael L Klein} } @article {2009|1469, title = {Molecular dynamics simulation of cooling: Heat transfer from a photoexcited peptide to the solvent}, journal = {J. Chem. Phys.}, volume = {131}, number = {18}, year = {2009}, month = {nov}, author = {Park, Sang-Min and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2008|1478, title = {MetaMol: High quality visualization of Molecular Skin Surface}, journal = {J. Mol. Graphics Modell.}, volume = {27}, number = {2}, year = {2008}, pages = {209{\textendash}213}, author = {Matthieu Chavent and B Levy and B Maigret} } @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|1829, title = {Molecular modeling and simulation of conjugated polymer oligomers: ground and excited state chain dynamics of PPV in the gas phase}, journal = {J. Phys. Chem. B}, volume = {112}, number = {16}, year = {2008}, pages = {4983{\textendash}93}, author = {Sterpone, Fabio and Rossky, Peter J} } @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 {2007|1535, title = {Monomer adds to preformed structured oligomers of A beta-peptides by a two-stage dock-lock mechanism}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {104}, number = {1}, year = {2007}, month = {jan}, pages = {111{\textendash}116}, author = {Phuong Hoang Nguyen and Li, Mai Suan and Stock, Gerhard and Straub, John E. and Thirumalai, D.} } @article {2006|1450, title = {Mapping a Homopolymer onto a Model Fluid}, journal = {J. Chem. Phys.}, volume = {125}, year = {2006}, pages = {064906}, author = {S. Pasquali and J.K. Percus} } @article {2006|1441, title = {Molecular modeling and simulation of water near model micelles: diffusion, rotational relaxation and structure at the hydration interface}, journal = {J. Phys. Chem. B}, volume = {110}, number = {23}, year = {2006}, pages = {11504{\textendash}10}, author = {Sterpone, Fabio and Marchetti, Gino and Pierleoni, Carlo and Marchi, Massimo} } @article {2005|2011, title = {{M}olecular tuning of fast gating in pentameric ligand-gated ion channels}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {102}, number = {50}, year = {2005}, month = {dec}, pages = {18207{\textendash}18212}, publisher = {National Acad Sciences}, author = {Grutter, T. and de Carvalho, L. P. and Dufresne, V. and Antoine Taly and Edelstein, S. J. and Jean-Pierre Changeux} } @article {2005|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 {2005|1508, title = {Modular RNA architecture revealed by computational analysis of existing pseudoknots and ribosomal RNAs}, journal = {Nuc. Acids Res.}, volume = {33}, year = {2005}, pages = {1384{\textendash}1398}, author = {S. Pasquali and H.H. Gan and T. Schlick} } @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 {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 {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 {2001|1853, title = {Molecular dynamics of minimal B-DNA}, journal = {J. Comput. Chem.}, volume = {22}, number = {4}, year = {2001}, pages = {457{\textendash}467}, author = {Alexey K Mazur} } @article {2001|1844, title = {Molecular dynamics studies of sequence-directed curvature in bending locus of Trypanosome kinetoplast DNA}, journal = {J. Biomol. Struct. Dyn.}, volume = {18}, number = {6}, year = {2001}, pages = {832{\textendash}843}, author = {Alexey K Mazur} } @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 {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} } @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|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 {1996|1660, title = {Molecular modelling study of the netropsin complexation with a nucleic acid triple helix}, journal = {J. Biomol. Struct. Dyn.}, volume = {14}, year = {1996}, month = {dec}, pages = {293{\textendash}302}, abstract = {

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

}, doi = {10.1080/07391102.1996.10508125}, author = {Vovelle, F and Chantal Pr{\'e}vost and Durand, M and Maurizot, J C} } @article {1993, title = {Multiple attack in the porcine pancreatic alpha-amylase hydrolysis of amylose and amylopectine}, journal = {Arch. Biochem. Biophys.}, volume = {306}, year = {1993}, pages = {29{\textendash}38}, author = {Alexey K Mazur and H. Nakatani} } @article {1992|1722, title = {Modeling of the possible binding modes of substrates in the active site of {Taka-Amylase A}}, journal = {Mol. Biol.}, volume = {26}, year = {1992}, pages = {292{\textendash}299}, author = {M. G. Petuhov and Alexey K Mazur} } @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 {1991|1762, title = {Molecular dynamics of polymers with fixed internal structure: Choice of models and methods}, journal = {Russ. J. Phys. Chem.}, volume = {65}, year = {1991}, pages = {2548{\textendash}2552}, author = {V. E. Dorofeyev and Alexey K Mazur} } @article {1988|1627, title = {Model of spatial random movement of depolymerase when interacting with the substrate}, journal = {Biophysics}, volume = {23}, year = {1988}, pages = {417{\textendash}421}, author = {Alexey K Mazur and M. G. Petukhov and L. A. Elyakova} } @article {1984, title = {Mathematical models of depolymerization of amylose by alpha-amylases}, journal = {Biopolymers}, volume = {23}, year = {1984}, pages = {1735{\textendash}1756}, author = {Alexey K Mazur} } @article {1984|1629, title = {Most probable distribution at enzyme depolymerization of polysaccharides}, journal = {Biopolymers}, volume = {23}, year = {1984}, pages = {859{\textendash}876}, author = {Alexey K Mazur} } @article {1982, title = {Mathematical modelling of endoglucanase-catalysed hydrolysis of a linear polysaccharide}, journal = {Mol. Biol.}, volume = {16}, year = {1982}, pages = {499{\textendash}510}, author = {L. A. Elyakova and Alexey K Mazur} }