Laboratoire de Biochimie Théorique
Présentation
The Laboratory of Theoretical Biochemistry (LBT) is one of five laboratories within Institut de Biologie Physico-Chimique (IBPC) in Paris.
LBT belongs to the French national research agency CNRS through its Institute of Chemistry, and is associated with Paris Diderot University. The laboratory was created at IBPC in 1958 as Laboratoire de Biochimie Théorique. Our field is theoretical and computational biochemistry, at the interface between biology, chemistry, physics, and computing.
Our strategic objectives are twofold: invent simulation algorithms to reproduce and predict physical properties of biomolecules either in vitro or in the cell, and understand the molecular or conformational factors responsible for the biological functions of living systems, and diseases. The equilibrium between these two aspects is the key point of the laboratory policy.
LBT is organized as a team of independent researchers with complementary interests and domains of expertise, both in method development and in biophysical, biochemical, and biomedical applications. Advances in each of these domains emerge from the association of different sets of researchers around individual projects.
Thèmes de recherche
Les axes de recherches du LBT se concentrent sur les développements méthodologiques et algorithmiques pour l’étude de la structure, la dynamique, la mécanique et les interactions des macromolécules biologiques.
Les objectifs sont donc d'utiliser les ordinateurs pour ouvrir des fenêtres vers le monde moléculaire, en aidant à comprendre les facteurs qui sous-tendent des faits expérimentaux, et en prédisant les propriétés et le comportement des molécules biologiques.
Equipes de recherche
Directeur : Marc Baaden
[hal-00880345] Blind prediction of interfacial water positions in CAPRI
Date: 5 11 月 2013 - 19:21
Desc: We report the first assessment of blind predictions of water positions at protein-protein interfaces, performed as part of the critical assessment of predicted interactions (CAPRI) community-wide experiment. Groups submitting docking predictions for the complex of the DNase domain of colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict the positions of interfacial water molecules using the method of their choice. The predictions-20 groups submitted a total of 195 models-were assessed by measuring the recall fraction of water-mediated protein contacts. Of the 176 high- or medium-quality docking models-a very good docking performance per se-only 44% had a recall fraction above 0.3, and a mere 6% above 0.5. The actual water positions were in general predicted to an accuracy level no better than 1.5 Å, and even in good models about half of the contacts represented false positives. This notwithstanding, three hotspot interface water positions were quite well predicted, and so was one of the water positions that is believed to stabilize the loop that confers specificity in these complexes. Overall the best interface water predictions was achieved by groups that also produced high-quality docking models, indicating that accurate modelling of the protein portion is a determinant factor. The use of established molecular mechanics force fields, coupled to sampling and optimization procedures also seemed to confer an advantage. Insights gained from this analysis should help improve the prediction of protein-water interactions and their role in stabilizing protein complexes.
[hal-01084644] Game on, science - how video game technology may help biologists tackle visualization challenges.
Date: 19 11 月 2014 - 16:56
Desc: The video games industry develops ever more advanced technologies to improve rendering, image quality, ergonomics and user experience of their creations providing very simple to use tools to design new games. In the molecular sciences, only a small number of experts with specialized know-how are able to design interactive visualization applications, typically static computer programs that cannot easily be modified. Are there lessons to be learned from video games? Could their technology help us explore new molecular graphics ideas and render graphics developments accessible to non-specialists? This approach points to an extension of open computer programs, not only providing access to the source code, but also delivering an easily modifiable and extensible scientific research tool. In this work, we will explore these questions using the Unity3D game engine to develop and prototype a biological network and molecular visualization application for subsequent use in research or education. We have compared several routines to represent spheres and links between them, using either built-in Unity3D features or our own implementation. These developments resulted in a stand-alone viewer capable of displaying molecular structures, surfaces, animated electrostatic field lines and biological networks with powerful, artistic and illustrative rendering methods. We consider this work as a proof of principle demonstrating that the functionalities of classical viewers and more advanced novel features could be implemented in substantially less time and with less development effort. Our prototype is easily modifiable and extensible and may serve others as starting point and platform for their developments. A webserver example, standalone versions for MacOS X, Linux and Windows, source code, screen shots, videos and documentation are available at the address: http://unitymol.sourceforge.net/.
[hal-01084652] Interactive Molecular Dynamics: Scaling up to Large Systems
Date: 19 11 月 2014 - 17:02
Desc: Combining molecular dynamics simulations with user interaction would have various applications in both education and research. By enabling interactivity the scientist will be able to visualize the experiment in real time and drive the simulation to a desired state more easily. However, interacting with systems of interesting size requires significant computing resources due to the complexity of the simulation. In this paper, we propose an approach to combine a classical parallel molecular dynamics simulator, Gromacs, to a 3D virtual reality environment allowing to steer the simulation through external user forces applied with an haptic device to a selection of atoms. We specifically focused on minimizing the intrusion in the simulator code, on efficient parallel data extraction and filtering to transfer only the necessary data to the visualization environment, and on a controlled asynchronism between various components to improve interactivity. We managed to steer molecular systems of 1.7 M atoms at about 25 Hz using 384 CPU cores. This framework allowed us to study a concrete scientific problem by testing one hypothesis of the transport of an iron complex from the exterior of the bacteria to the periplasmic space through the FepA membrane protein.
[hal-00942627] ExaViz: a Flexible Framework to Analyse, Steer and Interact with Molecular Dynamics Simulations
Date: 23 5 月 2014 - 10:56
Desc: The amount of data generated by molecular dynamics simulations of large molecular assemblies and the sheer size and complexity of the systems studied call for new ways to analyse, steer and interact with such calculations. Traditionally, the analysis is performed off-line once the huge amount of simulation results have been saved to disks, thereby stressing the supercomputer I/O systems, and making it increasingly difficult to handle post-processing and analysis from the scientist's office. The ExaViz framework is an alternative approach developed to couple the simulation with analysis tools to process the data as close as possible to their source of creation, saving a reduced, more manageable and pre-processed data set to disk. ExaViz supports a large variety of analysis and steering scenarios. Our framework can be used for live sessions (simulations short enough to be fully followed by the user) as well as batch sessions (long time batch executions). During interactive sessions, at run time, the user can display plots from analysis, visualise the molecular system and steer the simulation with a haptic device. We also emphasise how a Cave-like immersive environment could be used to leverage such simulations, offering a large display surface to view and intuitively navigate the molecular system.
[hal-02999198] Proteomic and functional mapping of cardiac Na V 1.5 channel phosphorylation reveals multisite regulation of surface expression and gating
Date: 10 11 月 2020 - 18:12
Desc: Phosphorylation of Na V 1.5 channels regulates cardiac excitability, yet the phosphorylation sites regulating channel function and the underlying mechanisms remain largely unknown. Using a systematic quantitative phosphoproteomic approach, we analyzed Na V 1.5 channel complexes purified from non-failing and failing mouse left ventricles, and we identified 42 phosphorylation sites on Na V 1.5. Most sites are clustered, and three of these clusters are highly phosphorylated. Analyses of phosphosilent and phosphomimetic Na V 1.5 mutants revealed the roles of three phosphosites in regulating Na V 1.5 channel expression and gating. The phosphorylated serines-664 and -667 regulate the voltage-dependence of channel activation in a cumulative manner, whereas phosphorylation of the nearby serine-671, which is increased in failing hearts, decreases cell surface Na V 1.5 expression and peak Na + current. No additional roles could be assigned to the other clusters of phosphosites. Taken together, the results demonstrate that ventricular Na V 1.5 is highly phosphorylated, and that the phosphorylation-dependent regulation of Na V 1.5-encoded channels is highly complex, site-specific and dynamic.
Autres contacts
Institut de Biologie Physico-Chimique (IBPC)
13, rue Pierre et Marie Curie
75252 PARIS CEDEX 05