@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|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|2161, title = {Enhanced Sampling Methods for Molecular Dynamics Simulations [Article v1.0]}, journal = {Living Journal of Computational Molecular Science}, volume = {4}, year = {2022}, month = {Dec.}, pages = {1583}, abstract = {

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

}, doi = {10.33011/livecoms.4.1.1583}, url = {https://livecomsjournal.org/index.php/livecoms/article/view/v4i1e1583}, author = {J{\'e}r{\^o}me H{\'e}nin and Leli{\`e}vre, Tony and Shirts, Michael R. and Valsson, Omar and Delemotte, Lucie} } @article {2021|2154, title = {Influences of ssDNA-RecA Filament Length on the Fidelity of Homologous Recombination}, journal = {Journal of Molecular Biology}, volume = {433}, year = {2021}, pages = {167143}, abstract = {

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

}, keywords = {biased random walk, D-loop turnover, Double-strand break repair, genomic rearrangement, multiple reversible intermediates}, issn = {0022-2836}, doi = {https://doi.org/10.1016/j.jmb.2021.167143}, url = {https://www.sciencedirect.com/science/article/pii/S0022283621003727}, author = {Claudia Danilowicz and Evan Vietorisz and Veronica Godoy-Carter and Chantal Pr{\'e}vost and Mara Prentiss} } @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|2125, title = {Impact of the Astaxanthin, Betanin, and EGCG Compounds on Small Oligomers of Amyloid Aβ Peptide.}, journal = {J Chem Inf Model}, volume = {60}, year = {2020}, month = {2020 Mar 23}, pages = {1399-1408}, abstract = {

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

}, issn = {1549-960X}, doi = {10.1021/acs.jcim.9b01074}, author = {Minh Hung, Huynh and Nguyen, Minh Tho and Tran, Phuong-Thao and Truong, Vi Khanh and Chapman, James and Quynh Anh, Le Huu and Philippe Derreumaux and Vu, Van V and Ngo, Son Tung} } @article {2019|2127, title = {C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ Tetramer in Solution: Intensive MD Study.}, journal = {ACS Omega}, volume = {4}, year = {2019}, month = {2019 Jun 30}, pages = {11066-11073}, abstract = {

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

}, issn = {2470-1343}, doi = {10.1021/acsomega.9b00992}, author = {Tung, Nguyen Thanh and Philippe Derreumaux and Vu, Van V and Nam, Pham Cam and Ngo, Son Tung} } @article {2019|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|2071, title = {Involvement of the GABAA receptor α subunit in the mode of action of etifoxine}, journal = {Pharmacological research}, volume = {145}, year = {2019}, pages = {104250}, author = {Mattei, C{\'e}sar and Antoine Taly and Soualah, Zineb and Saulais, Oph{\'e}lie and Henrion, Daniel and Gu{\'e}rineau, Nathalie C and Verleye, Marc and Legros, Christian} } @article {2019|2128, title = {Probable Transmembrane Amyloid α-Helix Bundles Capable of Conducting Ca Ions.}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {2019 Mar 28}, pages = {2645-2653}, abstract = {

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

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.8b10792}, author = {Ngo, Son Tung and Philippe Derreumaux and Vu, Van V} } @inbook {2018|2085, title = {Applications to water transport systems: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {389-414}, issn = {1364-5498}, doi = {10.1039/c8fd90022a}, author = {Marc Baaden and Barboiu, Mihail and Borthakur, Manash Pratim and Chen, Chun-Long and Coalson, Rob and Davis, Jeffery and Freger, Viatcheslav and Gong, Bing and H{\'e}lix-Nielsen, Claus and Hickey, Robert and Hinds, Bruce and Hirunpinyopas, Wisit and Horner, Andreas and Hou, Jun-Li and Hummer, Gerhard and Iamprasertkun, Pawin and Kazushi, Kinbara and Kumar, Manish and Legrand, Yves-Marie and Lokesh, Mahesh and Mi, Baoxia and Mitra, Sushanta and Murail, Samuel and Noy, Aleksandr and Nunes, Suzana and Pohl, Peter and Song, Qilei and Song, Woochul and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish} } @inbook {2018|2082, title = {Biomimetic water channels: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {205-229}, issn = {1364-5498}, doi = {10.1039/c8fd90020e}, author = {Marc Baaden and Barboiu, Mihail and Bill, Roslyn M and Chen, Chun-Long and Davis, Jeffery and Di Vincenzo, Maria and Freger, Viatcheslav and Fr{\"o}ba, Michael and Gale, Philip A and Gong, Bing and H{\'e}lix-Nielsen, Claus and Hickey, Robert and Hinds, Bruce and Hou, Jun-Li and Hummer, Gerhard and Kumar, Manish and Legrand, Yves-Marie and Lokesh, Mahesh and Mi, Baoxia and Murail, Samuel and Pohl, Peter and Sansom, Mark and Song, Qilei and Song, Woochul and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish and V{\"o}gele, Martin} } @article {2018|2112, title = {Breaking down cellulose fibrils with a mid-infrared laser}, journal = {Cellulose}, volume = {25}, year = {2018}, pages = {5553{\textendash}5568}, author = {Domin, Dominik and Man, Viet Hoang and Van-Oanh, Nguyen-Thi and Wang, Junmei and Kawasaki, Takayasu and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2018|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} } @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|2111, title = {Molecular mechanism of the cell membrane pore formation induced by bubble stable cavitation}, journal = {The Journal of Physical Chemistry B}, volume = {123}, year = {2018}, pages = {71{\textendash}78}, author = {Man, Viet Hoang and Truong, Phan Minh and Li, Mai Suan and Wang, Junmei and Van-Oanh, Nguyen-Thi and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2018|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|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} } @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} } @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|2020, title = {Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {May}, pages = {1858}, author = {Colloc{\textquoteright}h, N. and S Sacquin-Mora and Avella, G. and Dhaussy, A. C. and Prange, T. and Vallone, B. and Girard, E.} } @article {2017|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 {2016|1759, title = {Great interactions: How binding incorrect partners can teach us about protein recognition and function}, journal = {Proteins: Struct., Funct., Bioinf.}, year = {2016}, pages = {n/a-n/a}, keywords = {binding sites prediction, coarse grain models, docking, protein-protein interaction, protein-protein interfaces}, issn = {1097-0134}, doi = {10.1002/prot.25086}, author = {Vamparys, Lydie and B. Laurent and Carbone, A. and S Sacquin-Mora} } @article {2016|1703, title = {Nonequilibrium all-atom molecular dynamics simulation of the bubble cavitation and application to dissociate amyloid fibrils}, journal = {J. Chem. Phys.}, volume = {145}, number = {17}, year = {2016}, month = {nov}, abstract = {The cavitation of gas bubbles in liquids has been applied to different disciplines in life and natural sciences, and in technologies. To obtain an appropriate theoretical description of effects induced by the bubble cavitation, we develop an all-atom nonequilibrium molecular-dynamics simulation method to simulate bubbles undergoing harmonic oscillation in size. This allows us to understand the mechanism of the bubble cavitation-induced liquid shear stress on surrounding objects. The method is then employed to simulate an A beta fibril model in the presence of bubbles, and the results show that the bubble expansion and contraction exert water pressure on the fibril. This yields to the deceleration and acceleration of the fibril kinetic energy, facilitating the conformational transition between local free energy minima, and leading to the dissociation of the fibril. Our work, which is a proof-of-concept, may open a new, efficient way to dissociate amyloid fibrils using the bubble cavitation technique, and new venues to investigate the complex phenomena associated with amyloidogenesis. Published by AIP Publishing.}, issn = {0021-9606}, doi = {10.1063/1.4966263}, author = {Man Hoang Viet and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2016|1733, title = {PEP-FOLD3: faster denovo structure prediction for linear peptides in solution and in complex}, journal = {Nucleic Acids Res.}, volume = {44}, number = {W1}, year = {2016}, pages = {W449-W454}, abstract = {Structure determination of linear peptides of 5-50 amino acids in aqueous solution and interacting with proteins is a key aspect in structural biology. PEP-FOLD3 is a novel computational framework, that allows both (i) de novo free or biased prediction for linear peptides between 5 and 50 amino acids, and (ii) the generation of native-like conformations of peptides interacting with a protein when the interaction site is known in advance. PEP-FOLD3 is fast, and usually returns solutions in a few minutes. Testing PEP-FOLD3 on 56 peptides in aqueous solution led to experimental-like conformations for 80\% of the targets. Using a benchmark of 61 peptide-protein targets starting from the unbound form of the protein receptor, PEP-FOLD3 was able to generate peptide poses deviating on average by 3.3 angstrom from the experimental conformation and return a native-like pose in the first 10 clusters for 52\% of the targets. PEP-FOLD3 is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD3.}, issn = {0305-1048}, doi = {10.1093/nar/gkw329}, author = {Lamiable, Alexis and Thevenet, Pierre and Rey, Julien and Vavrusa, Marek and Philippe Derreumaux and Pierre Tuffery} } @article {2016|1744, title = {Picosecond infrared laser-induced all-atom nonequilibrium molecular dynamics simulation of dissociation of viruses}, journal = {Phys. Chem. Chem. Phys.}, volume = {18}, number = {17}, year = {2016}, month = {may}, pages = {11951{\textendash}11958}, abstract = {Since the discovery of the plant pathogen tobacco mosaic virus as the first viral entity in the late 1800s, viruses traditionally have been mainly thought of as pathogens for disease-resistances. However, viruses have recently been exploited as nanoplatforms with applications in biomedicine and materials science. To this aim, a large majority of current methods and tools have been developed to improve the physical stability of viral particles, which may be critical to the extreme physical or chemical conditions that viruses may encounter during purification, fabrication processes, storage and use. However, considerably fewer studies are devoted to developing efficient methods to degrade or recycle such enhanced stability biomaterials. With this in mind, we carry out all-atom nonequilibriummolecular dynamics simulation, inspired by the recently developed mid-infrared free-electron laser pulse technology, to dissociate viruses. Adopting the poliovirus as a representative example, we find that the primary step in the dissociation process is due to the strong resonance between the amide I vibrational modes of the virus and the tuned laser frequencies. This process is determined by a balance between the formation and dissociation of the protein shell, reflecting the highly plasticity of the virus. Furthermore, our method should provide a feasible approach to simulate viruses, which is otherwise too expensive for conventional equilibrium all-atom simulations of such very large systems. Our work shows a proof of concept which may open a new, efficient way to cleave or to recycle virus-based materials, provide an extremely valuable tool for elucidating mechanical aspects of viruses, and may well play an important role in future fighting against virus-related diseases.}, issn = {1463-9076}, doi = {10.1039/c5cp07711g}, author = {Viet Hoang Man and Van-Oanh, Nguyen-Thi and Philippe Derreumaux and Li, Mai Suan and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2016|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|1764, title = {Thermal activation of {\textquoteleft}allosteric-like{\textquoteright} large-scale motions in a eukaryotic Lactate Dehydrogenase.}, journal = {Sci. Reports}, volume = {7}, year = {2016}, pages = {41092}, author = {M. Katava and M. Maccarini and G. Villain and A. Paciaroni and M. Sztucki and O. Ivanova and D. Madern and Fabio Sterpone} } @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|1768, title = {Communication: Multiple atomistic force fields in a single enhanced sampling simulation.}, journal = {The Journal of Chemical Physics}, volume = {143}, number = {2}, year = {2015}, month = {jul}, pages = {021101{\textendash}021101}, doi = {10.1063/1.4926535}, author = {Hoang Viet, Man and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2015|1704, title = {Communication: Multiple atomistic force fields in a single enhanced sampling simulation}, journal = {J. Chem. Phys.}, volume = {143}, number = {2}, year = {2015}, month = {jul}, pages = {021101}, doi = {10.1063/1.4926535}, author = {Man Hoang Viet and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2015|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|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|1705, title = {Picosecond dissociation of amyloid fibrils with infrared laser: A nonequilibrium simulation study}, journal = {J. Chem. Phys.}, volume = {143}, number = {15}, year = {2015}, month = {oct}, pages = {155101}, doi = {10.1063/1.4933207}, author = {Man Hoang Viet and Philippe Derreumaux and Mai Suan Li and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2015|1745, title = {Picosecond melting of peptide nanotubes using an infrared laser: a nonequilibrium simulation study}, journal = {Phys. Chem. Chem. Phys.}, volume = {17}, number = {41}, year = {2015}, pages = {27275{\textendash}27280}, doi = {10.1039/c5cp04401d}, author = {Viet, Man Hoang and Phan Minh Truong and Philippe Derreumaux and Li, Mai Suan and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @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} } @article {2014|1379, title = {Effect of the English Familial Disease Mutation (H6R) on the Monomers and Dimers of A beta 40 and A beta 42}, journal = {Acs Chem. Neurosci.}, volume = {5}, number = {8}, year = {2014}, month = {aug}, pages = {646{\textendash}657}, author = {Man Hoang Viet and Phuong Hoang Nguyen and Philippe Derreumaux and Li, Mai Suan} } @article {2013, title = {Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of A beta(40) and A beta(42)}, journal = {Acs Chem. Neurosci.}, volume = {4}, number = {11}, year = {2013}, month = {nov}, pages = {1446{\textendash}1457}, author = {Man Hoang Viet and Phuong Hoang Nguyen and Son Tung Ngo and Li, Mai Suan and Philippe Derreumaux} } @article {2013|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.} } @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 {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|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|1748, title = {Optimizing the design of oligonucleotides for homology directed gene targeting}, journal = {Plos One}, volume = {6}, year = {2011}, pages = {e14795}, abstract = {

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

}, doi = {10.1371/journal.pone.0014795}, author = {Min{\'e}-Hattab, Judith and Fleury, Genevi{\`e}ve and Chantal Pr{\'e}vost and Dutreix, Marie and Viovy, Jean-Louis} } @article {2011|1691, title = {On the reorientation and hydrogen-bond dynamics of Alcohols}, journal = {J. Phys. Chem. B}, volume = {115}, year = {2011}, pages = {12173{\textendash}12178}, abstract = {

The mechanism of the OH bond reorientation in liquid methanol and ethanol is examined. It is found that the extended jump model, recently developed for water, describes the OH reorientation in these liquids. The slower reorientational dynamics in these alcohols compared to water can be explained by two key factors. The alkyl groups on the alcohol molecules exclude potential partners for hydrogen bonding exchanges, an effect that grows with the size of the alkyl chain. This increases the importance of the reorientation of intact hydrogen bonds, which also slows with increasing size of the alcohol and becomes the dominant reorientation pathway.

}, issn = {15206106}, author = {Vartia, Anthony A. and Mitchell-Koch, Katie R. and Guillaume Stirnemann and Laage, Damien and Thompson, Ward H.} } @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|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} } @article {2010|1457, title = {{A}tomic structure and dynamics of pentameric ligand-gated ion channels: new insight from bacterial homologues}, journal = {J. Physiol. (lond.)}, volume = {588}, year = {2010}, month = {feb}, pages = {565{\textendash}572}, author = {Corringer, P. J. and Marc Baaden and Bocquet, N. and Delarue, M. and Dufresne, V. and Nury, H. and Prevost, M. and Van Renterghem, C.} } @article {2010, title = {The VLITL aggregation-prone motif might trigger amyloid fibril formation of fibrinogen A alpha-chain frameshift variants in vivo}, journal = {Amyloid-journal of Protein Folding Disorders}, volume = {17}, number = {Suppl. 1}, year = {2010}, note = {12th International Symposium on Amyloidosis from Molecular Mechanisms Toward the Cure of Systemic Amyloidoses, Rome, ITALY, APR 18-21, 2010}, pages = {96{\textendash}97}, author = {Valleix, S. and Philippe Derreumaux and Garnier, C. and Briki, F. and Boimard, M. and Doucet, J. and Rioux-Leclercq, N. and Martin, L. and Grateau, G. and Delpech, M. and Le Pogamp, P.} } @article {2009|1442, title = {{C}harge {R}ecombination {K}inetics and {P}rotein {D}ynamics in {W}ild {T}ype and {C}arotenoid-less {B}acterial {R}eaction {C}enters: {S}tudies in {T}rehalose {G}lasses}, journal = {J. Phys. Chem. B}, volume = {113}, year = {2009}, month = {jul}, pages = {10389{\textendash}1398}, author = {Francia, F. and Malferrari, M. and S Sacquin-Mora and Venturoli, G.} } @book {2009|1567, title = {Coarse-graining protein mechanics}, volume = {Coarse-Graining of Condensed Phase and Biomolecular Systems}, year = {2009}, publisher = {Taylor and Francis}, organization = {Taylor and Francis}, author = {R Lavery and S Sacquin-Mora}, editor = {G. Voth} } @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} } @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 {2005|1631, title = {{A} chimera encoding the fusion of an acetylcholine-binding protein to an ion channel is stabilized in a state close to the desensitized form of ligand-gated ion channels}, journal = {C. R. Biol.}, volume = {328}, number = {3}, year = {2005}, month = {mar}, pages = {223{\textendash}234}, author = {Grutter, T. and Prado de Carvalho, L. and Virginie, D. and Antoine Taly and Fischer, M. and Jean-Pierre Changeux} } @article {2002, title = {Analysis of Protein Sequence/Structure Similarity Relationships}, journal = {Biophys. J.}, volume = {83}, year = {2002}, pages = {2781{\textendash}2791}, author = {H. H. Gan and R. A. Perow and S. Roy and J. Ko, M. Wu, J. Huang and S. Yan and A. Nicoletta and J. Vafai, D. Sun and L. Wang and J. E. Noah and S. Pasquali and T. Schlick} } @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 {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 {1996|1660, title = {Molecular modelling study of the netropsin complexation with a nucleic acid triple helix}, journal = {J. Biomol. Struct. Dyn.}, volume = {14}, year = {1996}, month = {dec}, pages = {293{\textendash}302}, abstract = {

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

}, doi = {10.1080/07391102.1996.10508125}, author = {Vovelle, F and Chantal Pr{\'e}vost and Durand, M and Maurizot, J C} } @article {1995|1869, title = {A NEW SPECTROSCOPIC MOLECULAR MECHANICS FORCE-FIELD - PARAMETERS FOR PROTEINS}, journal = {J. Chem. Phys.}, volume = {102}, number = {21}, year = {1995}, month = {jun}, pages = {8586{\textendash}8605}, doi = {10.1063/1.468848}, author = {Philippe Derreumaux and VERGOTEN, G} } @article {1995|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 {1995|1898, title = {A VIBRATIONAL MOLECULAR-FORCE FIELD OF MODEL COMPOUNDS WITH BIOLOGICAL INTEREST .4. PARAMETERS FOR THE DIFFERENT GLYCOSIDIC LINKAGES OF OLIGOSACCHARIDES}, journal = {J. Comput. Chem.}, volume = {16}, number = {2}, year = {1995}, month = {feb}, pages = {188{\textendash}199}, doi = {10.1002/jcc.540160206}, author = {Dauchez, M and Philippe Derreumaux and LAGANT, P and VERGOTEN, G} } @article {1994|1992, title = {FORCE-FIELD AND VIBRATIONAL-SPECTRA OF OLIGOSACCHARIDES WITH DIFFERENT GLYCOSIDIC LINKAGES .1. TREHALOSE DIHYDRATE, SOPHOROSE MONOHYDRATE AND LAMINARIBIOSE}, journal = {Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy}, volume = {50}, number = {1}, year = {1994}, month = {jan}, pages = {87{\textendash}104}, doi = {10.1016/0584-8539(94)80117-7}, author = {Dauchez, M and Philippe Derreumaux and LAGANT, P and VERGOTEN, G and SEKKAL, M and LEGRAND, P} } @article {1994|1993, title = {FORCE-FIELD AND VIBRATIONAL-SPECTRA OF OLIGOSACCHARIDES WITH DIFFERENT GLYCOSIDIC LINKAGES .2. MALTOSE MONOHYDRATE, CELLOBIOSE AND GENTIOBIOSE}, journal = {Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy}, volume = {50}, number = {1}, year = {1994}, month = {jan}, pages = {105{\textendash}118}, doi = {10.1016/0584-8539(94)80118-5}, author = {Dauchez, M and LAGANT, P and Philippe Derreumaux and VERGOTEN, G and SEKKAL, M and SOMBRET, B} } @article {1994|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|1909, title = {THE USE OF THE SPASIBA SPECTROSCOPIC POTENTIAL FOR REPRODUCING THE STRUCTURES AND VIBRATIONAL FREQUENCIES OF A SERIES OF ACIDS - ACETIC-ACID, PIVALIC ACID, SUCCINIC ACID, ADIPIC ACID AND L-GLUTAMIC ACID}, journal = {J. Mol. Struct.}, volume = {317}, number = {1-2}, year = {1994}, month = {jan}, pages = {171{\textendash}184}, doi = {10.1016/0022-2860(93)07860-Y}, author = {CHHIBA, M and Philippe Derreumaux and VERGOTEN, G} } @article {1993|1907, title = {COMPARISON OF THE IR AND RAMAN VIBRATIONAL FREQUENCIES AND INTENSITIES OF ALKANES USING THE AMBER AND SPASIBA FORCE-FIELDS - APPLICATION TO ETHANE, AND GAUCHE-N-BUTANE AND TRANS-N-BUTANE}, journal = {J. Mol. Struct.}, volume = {295}, year = {1993}, month = {may}, pages = {223{\textendash}232}, doi = {10.1016/0022-2860(93)85022-M}, author = {Philippe Derreumaux and LAGANT, P and VERGOTEN, G} } @article {1993|1908, title = {HARMONIC AND MOLECULAR-DYNAMICS OF N-OCTANE - COMPARISON BETWEEN THE AMBER AND SPASIBA FORCE-FIELDS}, journal = {J. Mol. Struct.}, volume = {295}, year = {1993}, month = {may}, pages = {233{\textendash}244}, doi = {10.1016/0022-2860(93)85023-N}, author = {Philippe Derreumaux and VERGOTEN, G} } @article {1993|1996, title = {INFLUENCE OF THE SPECTROSCOPIC POTENTIAL-ENERGY FUNCTION SPASIBA ON MOLECULAR-DYNAMICS OF PROTEINS - COMPARISON WITH THE AMBER POTENTIAL}, journal = {Theochem-journal of Molecular Structure}, volume = {105}, year = {1993}, month = {oct}, pages = {55{\textendash}64}, author = {Philippe Derreumaux and VERGOTEN, G} } @article {1993|1906, title = {THE STRUCTURES AND VIBRATIONAL FREQUENCIES OF A SERIES OF ALKANES USING THE SPASIBA FORCE-FIELD}, journal = {J. Mol. Struct.}, volume = {295}, year = {1993}, month = {may}, pages = {203{\textendash}221}, doi = {10.1016/0022-2860(93)85021-L}, author = {Philippe Derreumaux and Dauchez, M and VERGOTEN, G} } @article {1993|1896, title = {VIBRATIONAL MOLECULAR-FORCE FIELD OF MODEL COMPOUNDS WITH BIOLOGIC INTEREST .2. HARMONIC DYNAMICS OF BOTH ANOMERS OF GLUCOSE IN THE CRYSTALLINE STATE}, journal = {J. Comput. Chem.}, volume = {14}, number = {3}, year = {1993}, month = {mar}, pages = {263{\textendash}277}, doi = {10.1002/jcc.540140303}, author = {Dauchez, M and Philippe Derreumaux and VERGOTEN, G} } @article {1991|1503, title = {{B}ase-pairing shift in the major groove of ({C}{A})n tracts by {B}-{D}{N}{A} crystal structures}, journal = {Nature}, volume = {354}, year = {1991}, month = {nov}, pages = {167{\textendash}170}, author = {Y Timsit and Vilbois, E. and Moras, D.} } @article {1991|1987, title = {EFFECT OF UREY-BRADLEY-SHIMANOUCHI FORCE-FIELD ON THE HARMONIC DYNAMICS OF PROTEINS}, journal = {Proteins-structure Function and Genetics}, volume = {11}, number = {2}, year = {1991}, pages = {120{\textendash}132}, doi = {10.1002/prot.340110205}, author = {Philippe Derreumaux and VERGOTEN, G} } @article {1991|1895, title = {THE USE OF ULTRAVIOLET RESONANCE RAMAN INTENSITIES TO TEST PROPOSED MOLECULAR-FORCE FIELDS FOR NUCLEIC-ACID BASES}, journal = {J. Comput. Chem.}, volume = {12}, number = {6}, year = {1991}, month = {jul}, pages = {731{\textendash}741}, doi = {10.1002/jcc.540120610}, author = {LAGANT, P and Philippe Derreumaux and VERGOTEN, G and PETICOLAS, W} } @article {1990|1929, title = {NORMAL-COORDINATE TREATMENT OF A NUCLEIC BASE PAIR MODEL IN ITS CRYSTALLINE STATE - 1-METHYLCYTOSINE-9-ETHYLGUANINE}, journal = {J. Raman Spectrosc.}, volume = {21}, number = {4}, year = {1990}, month = {apr}, pages = {215{\textendash}226}, doi = {10.1002/jrs.1250210402}, author = {LAGANT, P and VERGOTEN, G and Philippe Derreumaux and DHENNIN, R} } @article {1990|1894, title = {A VIBRATIONAL MOLECULAR-FORCE FIELD OF MODEL COMPOUNDS WITH BIOLOGICAL INTEREST .1. HARMONIC DYNAMICS OF CRYSTALLINE UREA AT 123-K}, journal = {J. Comput. Chem.}, volume = {11}, number = {5}, year = {1990}, month = {jun}, pages = {560{\textendash}568}, doi = {10.1002/jcc.540110504}, author = {Philippe Derreumaux and VERGOTEN, G and LAGANT, P} } @article {1989|1912, title = {CONFORMATIONAL STUDIES OF NEUROACTIVE LIGANDS .1. FORCE-FIELD AND VIBRATIONAL-SPECTRA OF CRYSTALLINE ACETYLCHOLINE}, journal = {J. Phys. Chem.}, volume = {93}, number = {4}, year = {1989}, month = {feb}, pages = {1338{\textendash}1350}, doi = {10.1021/j100341a033}, author = {Philippe Derreumaux and WILSON, KJ and VERGOTEN, G and PETICOLAS, WL} } @article {1989|1913, title = {CONFORMATIONAL STUDIES OF NEUROACTIVE LIGANDS .2. SOLUTION-STATE CONFORMATIONS OF ACETYLCHOLINE}, journal = {J. Phys. Chem.}, volume = {93}, number = {4}, year = {1989}, month = {feb}, pages = {1351{\textendash}1357}, doi = {10.1021/j100341a034}, author = {WILSON, KJ and Philippe Derreumaux and VERGOTEN, G and PETICOLAS, WL} } @article {1989|1796, title = {RAMAN-SPECTROSCOPY, MOLECULAR-FORCE FIELDS, AND THE DYNAMICS OF BIOLOGICAL MOLECULES}, journal = {Chemica Scripta}, volume = {29A}, year = {1989}, month = {sep}, pages = {113{\textendash}122}, author = {PETICOLAS, WL and WILSON, KJ and Philippe Derreumaux and VERGOTEN, G} } @article {1988|1625, title = {Uv Resonance Raman-spectra and Solution State Conformations of Cholinergic Neurotransmitters}, journal = {Biophys. J.}, volume = {53}, number = {2}, year = {1988}, month = {feb}, pages = {A287-A287}, author = {WILSON, K. J. and Philippe Derreumaux and VERGOTEN, G. and W. L. Peticolas} }