Curvature as a Collective Coordinate in Enhanced Sampling Membrane Simulations

International audienceThe plasticity of membranes plays an important functional role in cells, cell components, and micelles, where bending, budding, and remodeling implement numerous recognition and communication processes. Comparatively, molecular simulation methods to induce, control, and quantitatively characterize such deformations remain scarce. This work defines a novel collective coordinate associated with membrane bending, which strives to combine realism (by preserving the notion of local atomic curvatures) and low computational cost (allowing its evaluation at every time step of a molecular dynamics simulation). Enhanced sampling simulations along this conformational coordinate provide convenient access to the underlying bending free energy landscape. To showcase its potential, the method is applied to three state-of-the-art problems: the determination of the bending free energy landscape of a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) bilayer, the formation of a POPE liposome, and the study of the influence of the Pseudomonas quinolone signal on the budding of Gram-negative bacterial outer membranes

Shelling the Voronoi interface of protein-protein complexes predicts residue activity and conservation

The accurate description of protein-protein interfaces remains a challenging task. Traditional criteria, based on atomic contacts or changes in solvent accessibility, tend to over or underpredict the interface itself and cannot discriminate active from less relevant parts. A recent simulation study by Mihalek and co-authors (2007, JMB 369, 584-95) concluded that active residues tend to be `dry', that is, insulated from water fluctuations. We show that patterns of `dry' residues can, to a large extent, be predicted by a fast, parameter-free and purely geometric analysis of protein interfaces. We introduce the shelling order of Voronoi facets as a straightforward quantitative measure of an atom's depth inside an interface. We analyze the correlation between Voronoi shelling order, dryness, and conservation on a set of 54 protein-protein complexes. Residues with high shelling order tend to be dry; evolutionary conservation also correlates with dryness and shelling order but, perhaps not surprisingly, is a much less accurate predictor of either property. Voronoi shelling order thus seems a meaningful and efficient descriptor of protein interfaces. Moreover, the strong correlation with dryness suggests that water dynamics within protein interfaces may, in first approximation, be described by simple diffusion models

Selectivity of pyoverdine recognition by the FpvA receptor of Pseudomonas aeruginosa from molecular dynamics simulations

International audienceThe Gram-negative bacterium Pseudomonas aeruginosa, a ubiquitous human opportunistic pathogen, has developed resistances to multiple antibiotics. It uses its primary native siderophore, pyoverdine, to scavenge the iron essential to its growth in the outside medium and transport it back into its cytoplasm. The FpvA receptor on the bacterial outer membrane recognizes and internalizes pyoverdine bearing its iron payload, but can also bind pyoverdines from other Pseudomonads or synthetic analogues. Pyoverdine derivatives could therefore be used as vectors to deliver antibiotics into the bacterium. In this study, we use molecular dynamics and free energy calculations to characterize the mechanisms and thermodynamics of the recognition of the native pyoverdines of P. aeruginosa and P. fluorescens by FpvA. Based on these results, we delineate the features that pyoverdines with high affinity for FpvA should possess. In particular, we show that (i) the dynamics and interaction of the unbound pyoverdines with water should be optimized with equal care as the interface contacts in the complex with FpvA; (ii) the C-terminal extremity of the pyoverdine chain, which appears to play no role in the bound complex, is involved in the intermediate stages of recognition; and (iii) the length and cyclicity of the pyoverdine chain can be used to fine-tune the kinetics of the recognition mechanism

Decoding the patterns of ubiquitin recognition by ubiquitin-associated domains from free energy simulations

International audienceUbiquitin is a highly conserved, highly represented protein acting as a regulating signal in numerous cellular processes. It leverages a single hydrophobic binding patch to recognize and bind a large variety of protein domains with remarkable specificity, but can also self-assemble into chains of poly-diubiquitin units in which these interfaces are sequestered, profoundly altering the individual monomers' recognition characteristics. Despite numerous studies, the origins of this varied specificity and the competition between substrates for the binding of the ubiquitin interface patch remain under heated debate. This study uses enhanced sampling all-atom molecular dynamics to simulate the unbinding of complexes of mono-or K48-linked diubiquitin bound to several ubiquitin-associated domains, providing insights into the mechanism and free energetics of ubiquitin recognition and binding. The implications for the subtle tradeoff between the stability of the polyubiquitin signal and its easy recognition by target protein assemblies are discussed, as is the enhanced affinity of the latter for long polyubiquitin chains compared to isolated mono-or diubiquitin

Caractérisation multi-échelle et analyse par essai d'indentation instrumentée de matériaux à gradient générés par procédés mécaniques et thermochimiques de traitement de surface

Cette thèse est un travail prospectif sur la caractérisation multi-échelle de matériaux à gradient de propriétés générés par des traitements de surface de type mécanique (grenaillage à air comprimé ou par ultrasons) ou thermochimique (nitruration, implantation ionique, cémentation basse température). Les apports de plusieurs techniques de caractérisation (microscopie électronique à balayage, spectrométrie, indentation instrumentée, microscopie interférométrique), à différentes échelles, et l existence possible d une signature des traitements de surface étudiés sur le matériau ont été examinés. Une analyse multi-échelle des échantillons grenaillés par ultrasons a permis d établir un lien entre les paramètres procédé et la rugosité du matériau. Une approche originale statistique a été proposée pour déterminer la dureté d un matériau modifié par un traitement de surface donné sans altérer la surface par une rectification. Elle a permis d établir un lien entre la rugosité des échantillons grenaillés par ultrasons et leur dureté. Une recherche bibliographique détaillée a été réalisée sur la simulation de l essai d indentation instrumentée par éléments finis en étudiant une centaine d articles afin d évaluer l influence des hypothèses des modèles sur leurs résultats. A l aide d un modèle éléments finis, la sensibilité des courbes d indentation à une variation des paramètres matériau a été examinée. Cela a permis de mettre en place une réflexion sur l identification des propriétés d un matériau à gradient à l aide de l essai d indentation.This thesis is a prospective work on the multiscale characterization of plastically graded materials obtained with mechanical (shot peening using air pressure or ultrasounds) or thermochemical (nitriding, ion implantation, low temperature carburizing) surface treatments. The benefits of several characterization techniques (scanning electron microscopy, spectrometry, instrumented indentation, interferometric microscopy), at different scales, and the possible existence of a signature of the studied surface treatments on the material were examined. A multiscale analysis of the ultrasonically shot-peened specimens linked the process conditions with the material roughness. A novel statistical approach was proposed to determine the treated material roughness without deteriorating the surface through resurfacing. The latter enabled to establish a link between the shot-peened specimen roughness and their hardness. A detailed literature review of a hundred articles examined the IV simulation of the instrumented indentation test with finite elements in order to assess the effect of different hypotheses on the simulation results. Using a finite element model, the sensitivity of indentation curves to a variation of material parameters was examined. The latter enabled to reflect on the identification of the properties of plastically grade materials using the instrumented indentation test.COMPIEGNE-BU (601592101) / SudocSudocFranceF

Synthesis of Tetragonal and Orthorhombic Polymorphs of Hf3N4 by High-Pressure Annealing of a Prestructured Nanocrystalline Precursor

Hf3N4 in nanocrystalline form is produced by solution phase reaction of Hf(NEtMe)4 with ammonia followed by low-temperature pyrolysis in ammonia. Understanding of phase behavior in these systems is important because early transition-metal nitrides with the metal in maximum oxidation state are potential visible light photocatalysts. A combination of synchrotron powder X-ray diffraction and pair distribution function studies has been used to show this phase to have a tetragonally distorted fluorite structure with 1/3 vacancies on the anion sites. Laser heating nanocrystalline Hf3N4 at 12 GPa and 1500 K in a diamond anvil cell results in its crystallization with the same structure type, an interesting example of prestructuring of the phase during preparation of the precursor compound. This metastable pathway could provide a route to other new polymorphs of metal nitrides and to nitrogen-rich phases where they do not currently exist. Importantly it leads to bulk formation of the material rather than surface conversion as often occurs in elemental combination reactions at high pressure. Laser heating at 2000 K at a higher pressure of 19 GPa results in a further new polymorph of Hf3N4 that adopts an anion deficient cottunite-type (orthorhombic) structure. The orthorhombic Hf3N4 phase is recoverable to ambient pressure and the tetragonal phase is at least partially recoverable

High-pressure investigations of CaTiO3 up to 60 GPa using X-ray diffraction and Raman spectroscopy

In this work, we investigate calcium titanate (CaTiO3 - CTO) using X-ray diffraction and Raman spectroscopy up to 60 and 55 GPa respectively. Both experiments show that the orthorhombic Pnma structure remains stable up to the highest pressures measured, in contradiction to ab-initio predictions. A fit of the compression data with a second-order Birch-Murnaghan equation of state yields a bulk modulus K0 of 181.0(6) GPa. The orthorhombic distortion is found to increase slightly with pressure, in agreement with previous experiments at lower pressures and the general rules for the evolution of perovskites under pressure. High-pressure polarized Raman spectra also enable us to clarify the Raman mode assignment of CTO and identify the modes corresponding to rigid rotation of the octahedra, A-cation shifts and Ti-O bond stretching. The Raman signature is then discussed in terms of compression mechanisms.Comment: 11 pages, 6 figures, 4 table

An algorithm to enumerate all possible protein conformations verifying a set of distance constraints

International audienceBackground: The determination of protein structures satisfying distance constraints is an important problem in structural biology. Whereas the most common method currently employed is simulated annealing, there have been other methods previously proposed in the literature. Most of them, however, are designed to find one solution only. Results: In order to explore exhaustively the feasible conformational space, we propose here an interval Branch-and-Prune algorithm (iBP) to solve the Distance Geometry Problem (DGP) associated to protein structure determination. This algorithm is based on a discretization of the problem obtained by recursively constructing a search space having the structure of a tree, and by verifying whether the generated atomic positions are feasible or not by making use of pruning devices. The pruning devices used here are directly related to features of protein conformations. Conclusions: We described the new algorithm iBP to generate protein conformations satisfying distance constraints, that would potentially allows a systematic exploration of the conformational space. The algorithm iBP has been applied on three α-helical peptides

Persistent Magnetic Wreaths in a Rapidly Rotating Sun

When our Sun was young it rotated much more rapidly than now. Observations of young, rapidly rotating stars indicate that many possess substantial magnetic activity and strong axisymmetric magnetic fields. We conduct simulations of dynamo action in rapidly rotating suns with the 3-D MHD anelastic spherical harmonic (ASH) code to explore the complex coupling between rotation, convection and magnetism. Here we study dynamo action realized in the bulk of the convection zone for a system rotating at three times the current solar rotation rate. We find that substantial organized global-scale magnetic fields are achieved by dynamo action in this system. Striking wreaths of magnetism are built in the midst of the convection zone, coexisting with the turbulent convection. This is a surprise, for it has been widely believed that such magnetic structures should be disrupted by magnetic buoyancy or turbulent pumping. Thus, many solar dynamo theories have suggested that a tachocline of penetration and shear at the base of the convection zone is a crucial ingredient for organized dynamo action, whereas these simulations do not include such tachoclines. We examine how these persistent magnetic wreaths are maintained by dynamo processes and explore whether a classical mean-field $\alpha$-effect explains the regeneration of poloidal field.Comment: 17 pages, 9 figures, 1 appendix, emulateapj format; published version of sections 3-4, 7 and appendix from arXiv:0906.240

Histoire de l’innovation et des technologies de l’information

Larissa Zakharova, maîtresse de conférencesYves Bouvier, maître de conférences à l’Université de SavoieLéonard Laborie, Valérie Schafer, chargés de recherche au CNRSStéphanie Le Gallic, allocataire-moniteur à l’Université Paris-SorbonneBenjamin Thierry, PRAG à l’IUFM Paris-Sorbonne Le séminaire a permis de mener une réflexion collective autour des technologies de l’information et de la communication, en s’intéressant aux acteurs de l’innovation (individuels et collectifs), à leurs interaction..