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-02373115] H1–nucleosome interactions and their functional implications
Date: 11 mai 2021 - 12:36
Desc: [...]
[hal-01498115] A novel Locally Closed Conformation of a Bacterial Pentameric Proton-gated Ion Channel
Date: 11 mai 2021 - 12:36
Desc: Pentameric ligand-gated ion channels mediate signal transduction through conformational transitions between closed-pore and open-pore states. To stabilize a closed conformation of GLIC, a bacterial proton-gated homolog from Gloeobacter violaceus whose open structure is known, we separately generated either four cross-links or two single mutations. We found all six mutants to be in the same 'locally closed' conformation using X-ray crystallography, sharing most of the features of the open form but showing a locally closed pore as a result of a concerted bending of all of its M2 helices. The mutants adopt several variant conformations of the M2-M3 loop, and in all cases an interacting lipid that is observed in the open form disappears. A single cross-linked mutant is functional, according to electrophysiology, and the locally closed structure of this mutant indicates that it has an increased flexibility. Further cross-linking, accessibility and molecular dynamics data suggest that the locally closed form is a functionally relevant conformation that occurs during allosteric gating transitions.
[hal-00645160] X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel.
Date: 11 mai 2021 - 12:36
Desc: General anaesthetics have enjoyed long and widespread use but their molecular mechanism of action remains poorly understood. There is good evidence that their principal targets are pentameric ligand-gated ion channels (pLGICs) such as inhibitory GABA(A) (γ-aminobutyric acid) receptors and excitatory nicotinic acetylcholine receptors, which are respectively potentiated and inhibited by general anaesthetics. The bacterial homologue from Gloeobacter violaceus (GLIC), whose X-ray structure was recently solved, is also sensitive to clinical concentrations of general anaesthetics. Here we describe the crystal structures of the complexes propofol/GLIC and desflurane/GLIC. These reveal a common general-anaesthetic binding site, which pre-exists in the apo-structure in the upper part of the transmembrane domain of each protomer. Both molecules establish van der Waals interactions with the protein; propofol binds at the entrance of the cavity whereas the smaller, more flexible, desflurane binds deeper inside. Mutations of some amino acids lining the binding site profoundly alter the ionic response of GLIC to protons, and affect its general-anaesthetic pharmacology. Molecular dynamics simulations, performed on the wild type (WT) and two GLIC mutants, highlight differences in mobility of propofol in its binding site and help to explain these effects. These data provide a novel structural framework for the design of general anaesthetics and of allosteric modulators of brain pLGICs.
[hal-01523850] Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography.
Date: 11 mai 2021 - 12:36
Desc: [...]
[hal-01722019] Meet-U: educating through research immersion
Date: 6 mai 2021 - 11:50
Desc: We present a new educational initiative, called Meet-U, that aims at training students to collaborativework in computational biology and at bridging the gap between education and research.Meet-U mimics the set up of collaborative research projects and takes advantage of the most populartools for collaborative work and of cloud computing. Students are grouped in teams of 4-5 peopleand 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 incompetition 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 researchseminars. This very unique combination of education and research is strongly motivating for thestudents and provides a formidable opportunity for a scientific community to unite and increase itsvisibility. We report on our experience with Meet-U in two French universities with master studentsin bioinformatics and modeling, with protein-protein docking as the subject of the course.Meet-U is easy to implement, virtually costs nothing and can be straightforwardly transferred to other fieldsand/or universities. All the information and data are available at http://www.meet-u.org.
Autres contacts
Institut de Biologie Physico-Chimique (IBPC)
13, rue Pierre et Marie Curie
75252 PARIS CEDEX 05
