@article {2022|2158, title = {Tripeptide loop closure: A detailed study of reconstructions based on Ramachandran distributions}, journal = {Proteins: Structure, Function, and Bioinformatics}, volume = {90}, year = {2022}, pages = {858-868}, abstract = {

Abstract Tripeptide loop closure (TLC) is a standard procedure to reconstruct protein backbone conformations, by solving a zero-dimensional polynomial system yielding up to 16 solutions. In this work, we first show that multiprecision is required in a TLC solver to guarantee the existence and the accuracy of solutions. We then compare solutions yielded by the TLC solver against tripeptides from the Protein Data Bank. We show that these solutions are geometrically diverse (up to Root mean square deviation with respect to the data) and sound in terms of potential energy. Finally, we compare Ramachandran distributions of data and reconstructions for the three amino acids. The distribution of reconstructions in the second angular space stands out, with a rather uniform distribution leaving a central void. We anticipate that these insights, coupled to our robust implementation in the Structural Bioinformatics Library ( https://sbl.inria.fr/doc/Tripeptide_loop_closure-user-manual.html), will help understanding the properties of TLC reconstructions, with potential applications to the generation of conformations of flexible loops in particular.

}, keywords = {protein loop conformations, Ramachandran diagrams, robust numerics, tripeptide loop closure, tripeptides}, doi = {https://doi.org/10.1002/prot.26281}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/prot.26281}, author = {O{\textquoteright}Donnell, Timoth{\'e}e and Robert, Charles H. and Cazals, Fr{\'e}d{\'e}ric} } @article {2020|2131, title = {Tau R3-R4 Domain Dimer of the Wild Type and Phosphorylated Ser356 Sequences. I. In Solution by Atomistic Simulations.}, journal = {J Phys Chem B}, year = {2020}, month = {2020 Mar 27}, abstract = {

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

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.0c00574}, author = {Philippe Derreumaux and Man, Viet Hoang and Wang, Junmei and Phuong Hoang Nguyen} } @article {2020|2124, title = {Temperature Unmasks Allosteric Propensity in a Thermophilic Malate Dehydrogenase via Dewetting and Collapse}, journal = {The Journal of Physical Chemistry B}, volume = {124}, year = {2020}, pages = {1001-1008}, doi = {10.1021/acs.jpcb.9b10776}, url = {https://doi.org/10.1021/acs.jpcb.9b10776}, author = {Katava, M. and Marchi, M. and Madern, D. and Sztucki, M. and Maccarini, M. and Sterpone, F.} } @article {2019|2105, title = {Tetrameric Aβ40 and Aβ42 β-Barrel Structures by Extensive Atomistic Simulations. II. In Aqueous Solution.}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {2019 Aug 08}, pages = {6750-6756}, abstract = {

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

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.9b05288}, author = {Phuong Hoang Nguyen and Campanera, Josep M and Ngo, Son Tung and Loquet, Antoine and Philippe Derreumaux} } @article {2019|2106, title = {Tetrameric Aβ40 and Aβ42 β-Barrel Structures by Extensive Atomistic Simulations. I. In a Bilayer Mimicking a Neuronal Membrane.}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {2019 May 02}, pages = {3643-3648}, abstract = {

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

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.9b01206}, author = {Phuong Hoang Nguyen and Campanera, Josep M and Ngo, Son Tung and Loquet, Antoine and Philippe Derreumaux} } @booklet {2018|2066, title = {Ten simple rules to create a serious game, illustrated with examples from structural biology}, year = {2018}, author = {Marc Baaden and Delalande, Olivier and Nicolas F{\'e}rey and Pasquali, Samuela and Waldisp{\"u}hl, J{\'e}r{\^o}me and Antoine Taly} } @article {2018|2138, title = {Three Weaknesses for Three Perturbations: Comparing Protein Unfolding Under Shear, Force, and Thermal Stresses}, journal = {J Phys Chem B}, volume = {122}, year = {2018}, month = {Dec}, pages = {11922-11930}, abstract = {

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

}, doi = {10.1021/acs.jpcb.8b08711}, author = {Languin-Catto{\"e}n, Olivier and Melchionna, Simone and Philippe Derreumaux and Guillaume Stirnemann and Sterpone, Fabio} } @article {2017|2026, title = {Tailoring protein nanomechanics with chemical reactivity}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {Jun}, pages = {15658}, abstract = {

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

}, doi = {10.1038/ncomms15658}, author = {Beedle, Amy E M and Mora, Marc and Lynham, Steven and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @article {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} } @conference {2016|1608, title = {Toward Microscopic Simulations of Proteins in Cell-Like Environments}, booktitle = {Biophys. J.}, volume = {110}, number = {3, 1}, year = {2016}, note = {60th Annual Meeting of the Biophysical-Society, Los Angeles, CA, FEB 27-MAR 02, 2016}, month = {feb}, pages = {386A}, publisher = {Biophys Soc}, organization = {Biophys Soc}, issn = {0006-3495}, author = {Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2015, title = {{T}aming molecular flexibility to tackle rare diseases}, journal = {Biochimie}, volume = {113}, year = {2015}, pages = {54{\textendash}58}, author = {Cubellis, M. V. and Marc Baaden and Andreotti, G.} } @article {2015|2000, title = {{T}he plastid terminal oxidase: its elusive function points to multiple contributions to plastid physiology}, journal = {Annu. Rev. Plant Biol.}, volume = {66}, number = {1}, year = {2015}, pages = {49{\textendash}74}, publisher = {Annual Reviews}, author = {Nawrocki, W. J. and Tourasse, N. J. and Antoine Taly and Rappaport, F. and Wollman, F. A.} } @article {2015|1414, title = {{T}hree-dimensional representations of complex carbohydrates and polysaccharides{\textendash}{S}weet{U}nity{M}ol: a video game-based computer graphic software}, journal = {Glycobiology}, volume = {25}, number = {5}, year = {2015}, month = {may}, pages = {483{\textendash}491}, author = {Perez, S. and Tubiana, T. and Imberty, A. and Marc Baaden} } @article {2014|1518, title = {{T}he weak, fluctuating, dipole moment of membrane-bound hydrogenase from {A}quifex aeolicus accounts for its adaptability to charged electrodes}, journal = {Phys. Chem. Chem. Phys.}, volume = {16}, number = {23}, year = {2014}, month = {may}, pages = {11318{\textendash}11322}, author = {Oteri, F and Ciaccafava, A and Poulpiquet, A and Marc Baaden and Lojou, E and S Sacquin-Mora} } @article {2014|1905, title = {Theoretical study of the NLO responses of some natural and unnatural amino acids used as probe molecules}, journal = {J. Mol. Model.}, volume = {20}, number = {8}, year = {2014}, month = {aug}, pages = {2388}, doi = {10.1007/s00894-014-2388-0}, author = {Derrar, S. N. and Sekkal-Rahal, M. and Philippe Derreumaux and Springborg, M.} } @article {2014|1645, title = {Type VI secretion and bacteriophage tail tubes share a common assembly pathway.}, journal = {Embo Rep.}, volume = {15}, year = {2014}, month = {mar}, pages = {315{\textendash}21}, abstract = {

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

}, keywords = {Amino Acid Sequence, Bacterial Secretion Systems, Escherichia coli, Escherichia coli Proteins, Molecular Sequence Data, Protein Binding, Protein Multimerization, Protein Structure, Tertiary, Virulence Factors}, issn = {1469-3178}, doi = {10.1002/embr.201337936}, author = {Brunet, Yannick R and J{\'e}r{\^o}me H{\'e}nin and Celia, Herv{\'e} and Cascales, Eric} } @article {2013|1814, title = {Towards Morse theory for point cloud data.}, journal = {Inria Tech Reports}, number = {8331}, year = {2013}, publisher = {Inria}, url = {http://hal.inria.fr/hal-00848753}, author = {F. Cazals and C. Mueller and C. Robert and A. Roth} } @article {2012|2016, title = {{T}hermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics}, journal = {J. R. Soc. Interface}, volume = {9}, number = {76}, year = {2012}, month = {nov}, pages = {2845{\textendash}2855}, doi = {10.1098/rsif.2012.0364}, author = {Stadler, A. M. and Garvey, C. J. and Bocahut, A. and S Sacquin-Mora and Digel, I. and Schneider, G. J. and Natali, F. and Artmann, G. M. and Zaccai, G.} } @article {2012|1805, title = {{T}ightening of the {A}{T}{P}-binding sites induces the opening of {P}2{X} receptor channels}, journal = {Embo J.}, volume = {31}, number = {9}, year = {2012}, month = {may}, pages = {2134{\textendash}2143}, author = {Jiang, R. and Antoine Taly and Lemoine, D. and Martz, A. and Cunrath, O. and Grutter, T.} } @article {2012|1816, title = {Theoretical study on a series of push-pull molecules grafted on methacrylate copolymers serving for nonlinear optics}, journal = {Int. J. Quantum Chem.}, volume = {112}, number = {15}, year = {2012}, month = {aug}, pages = {2735{\textendash}2742}, doi = {10.1002/qua.23299}, author = {Derrar, S. N. and Sekkal-Rahal, M. and Guemra, K. and Philippe Derreumaux} } @article {2012|1795, title = {Thermophilic proteins: insight and perspective from in silico experiments}, journal = {Chem. Soc. Rev.}, volume = {41}, year = {2012}, pages = {1665{\textendash}1676}, publisher = {The Royal Society of Chemistry}, abstract = {Proteins from thermophilic and hyperthermophilic organisms are stable and function at high temperatures (50-100 [degree]C). The importance of understanding the microscopic mechanisms underlying this thermal resistance is twofold: it is key for acquiring general clues on how proteins maintain their fold stable and for targeting those medical and industrial applications that aim at designing enzymes that can work under harsh conditions. In this tutorial review we first provide the general background of protein thermostability by specifically focusing on the structural and thermodynamic peculiarities; next{,} we discuss how computational studies based on Molecular Dynamics simulations can broaden and refine our knowledge on such special class of proteins.}, author = {Sterpone, Fabio and Melchionna, Simone} } @article {2012|1740, title = {Torque transfer coefficient in DNA under torsional stress}, journal = {Phys. Rev. E}, volume = {86}, year = {2012}, pages = {011914}, author = {Alexey K Mazur} } @article {2010|1444, title = {{T}he molecular recognition mechanism for superoxide dismutase presequence binding to the mitochondrial protein import receptor {T}om20 from {O}ryza sativa involves an {L}{R}{T}{L}{A} motif}, journal = {J. Phys. Chem. B}, volume = {114}, year = {2010}, month = {nov}, pages = {13839{\textendash}13846}, author = {Y. Zhang and Marc Baaden and J. Yan and J. Shao and S. Qiu and Y. Wu and Y. Ding} } @article {2010|1457, title = {{A}tomic structure and dynamics of pentameric ligand-gated ion channels: new insight from bacterial homologues}, journal = {J. Physiol. (lond.)}, volume = {588}, year = {2010}, month = {feb}, pages = {565{\textendash}572}, author = {Corringer, P. J. and Marc Baaden and Bocquet, N. and Delarue, M. and Dufresne, V. and Nury, H. and Prevost, M. and Van Renterghem, C.} } @article {2009|1986, title = {Targeting the early steps of A beta 16-22 protofibril disassembly by N-methylated inhibitors: A numerical study}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {75}, number = {2}, year = {2009}, month = {may}, pages = {442{\textendash}452}, doi = {10.1002/prot.22254}, author = {Y Chebaro and Philippe Derreumaux} } @article {2009|2019, title = {Thermodynamics and dynamics of amyloid peptide oligomerization are sequence dependent}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {75}, number = {4}, year = {2009}, month = {jun}, pages = {954{\textendash}963}, keywords = {Amino Acid Sequence, Amyloid beta-Protein, beta 2-Microglobulin, Cluster Analysis, Computer Simulation, Models, Molecular, Peptide Fragments, Protein Multimerization, Protein Structure, Secondary, Structure-Activity Relationship, Thermodynamics}, doi = {10.1002/prot.22305}, author = {Lu, Yan and Philippe Derreumaux and Guo, Zhi and Mousseau, Normand and Wei, Guanghong} } @article {2007|1547, title = {{T}he 1.3 {A} resolution structure of the {R}{N}{A} tridecamer r({G}{C}{G}{U}{U}{U}{G}{A}{A}{A}{C}{G}{C}): metal ion binding correlates with base unstacking and groove contraction}, journal = {Rna}, volume = {13}, year = {2007}, month = {dec}, pages = {2098{\textendash}2107}, author = {Y Timsit and Bombard, S.} } @inbook {2007|1564, title = {There{\textquoteright}s plenty of room in the middle: multi-scale modelling of biological systems}, year = {2007}, pages = {173{\textendash}195}, publisher = {Research signpost, India}, organization = {Research signpost, India}, chapter = {Recent Advances in Protein engineering}, address = {Trivandrum, Kerala, India}, author = {Marc Baaden and R. Lavery}, editor = {A.G. de Brevern} } @article {2007|1477, title = {Three hydrolases and a transferase: Comparative analysis of active-site dynamics via the BioSimGrid database}, journal = {Journal of Molecular Graphics \& Modelling}, volume = {25}, number = {6}, year = {2007}, month = {mar}, pages = {896{\textendash}902}, author = {Tai, Kaihsu and Marc Baaden and Murdock, Stuart and Wu, Bing and Ng, Muan Hong and Johnston, Steven and Boardman, Richard and Fangohr, Hans and Cox, Katherine and Essex, Jonathan W. and Sansom, Mark S. P.} } @article {2004|1718, title = {Temperature dehydration of C12E6 micelle}, journal = {Langmuir}, volume = {20}, year = {2004}, pages = {4311{\textendash}4314}, author = {Fabio Sterpone and C. Pierleoni and G. Briganti and M. Marchi} } @article {2004|1878, title = {Torsion-induced phase transitions in fluids confined between chemically decorated substrates}, journal = {J. Chem. Phys.}, volume = {121}, number = {18}, year = {2004}, month = {nov}, pages = {9077{\textendash}9086}, doi = {10.1063/1.1804154}, author = {S Sacquin-Mora and Fuchs, AH and Schoen, M} } @article {2003|1548, title = {Theoretical studies on lanthanide cation extraction by picolinamides: Ligand-cation interactions and interfacial behavior}, journal = {Solvent Extr. Ion Exch.}, volume = {21}, number = {2}, year = {2003}, pages = {199{\textendash}220}, author = {Marc Baaden and Berny, F and Madic, C and Schurhammer, R and Wipff, G} } @article {2003|1838, title = {Titration {\em in silico} of reversible {B${\l}eftrightarrow$A} transitions in {DNA}}, journal = {J. Am. Chem. Soc.}, volume = {125}, number = {26}, year = {2003}, pages = {7849{\textendash}7859}, author = {Alexey K Mazur} } @article {2002|1650, title = {{T}he {D}{M}{P}{C} lipid phase transition influences differently the first and the second electron transfer reactions in bacterial reaction centers}, journal = {Febs Lett.}, volume = {532}, number = {1-2}, year = {2002}, month = {dec}, pages = {91{\textendash}96}, author = {Antoine Taly and Baciou, L. and Sebban, P.} } @article {2001|1482, title = {TBP at the water-oil interface: The effect of TBP concentration and water acidity investigated by molecular dynamics simulations}, journal = {J. Phys. Chem. B}, volume = {105}, number = {45}, year = {2001}, month = {nov}, pages = {11131{\textendash}11141}, author = {Marc Baaden and Burgard, M and Wipff, G} } @article {2000|1836, title = {Theoretical studies of the possible origin of intrinsic static bends in double helical DNA}, journal = {J. Am. Chem. Soc.}, volume = {122}, number = {51}, year = {2000}, pages = {12778{\textendash}12785}, author = {Alexey K Mazur} } @article {1994|1968, title = {Three-dimensional structure of extended chromatin fibers as revealed by tapping-mode scanning force microscopy}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {91}, number = {24}, year = {1994}, month = {nov}, pages = {11621{\textendash}11625}, abstract = {Unfixed chicken erythrocyte chromatin fibers in very low salt have been imaged with a scanning force microscope operating in the tapping mode in air at ambient humidity. These images reveal a three-dimensional organization of the fibers. The planar "zig-zag" conformation is rare, and extended "beads-on-a-string" fibers are seen only in chromatin depleted of histones H1 and H5. Glutaraldehyde fixation reveals very similar structures. Fibers fixed in 10 mM salt appear somewhat more compacted. These results, when compared with modeling studies, suggest that chromatin fibers may exist as irregular three-dimensional arrays of nucleosomes even at low ionic strength.}, keywords = {Animals, Atomic Force, Biological, Chickens, Chromatin, Fixatives, Histones, Microscopy, Models, Non-P.H.S., Non-U.S. Gov{\textquoteright}t, Osmolar Concentration, P.H.S., Research Support, Sodium Chloride, U.S. Gov{\textquoteright}t}, author = {S. H. Leuba and G. Yang and C. Robert and B. Samori and K. van Holde and J. Zlatanova and C. Bustamante} } @article {1994|1897, title = {A TRUNCATED NEWTON MINIMIZER ADAPTED FOR CHARMM AND BIOMOLECULAR APPLICATIONS}, journal = {J. Comput. Chem.}, volume = {15}, number = {5}, year = {1994}, month = {may}, pages = {532{\textendash}552}, doi = {10.1002/jcc.540150506}, author = {Philippe Derreumaux and ZHANG, GH and SCHLICK, T and BROOKS, B} } @article {1990|1724, title = {Toward a theory of quasi-steady-state enzymatic processes}, journal = {Mol. Biol.}, volume = {24}, year = {1990}, pages = {202{\textendash}208}, author = {Alexey K Mazur} }