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-01722019] Meet-U: educating through research immersion
Date: 15 jan 2021 - 14:32
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.
[halshs-02424173] Itinéraires Bis
Date: 15 jan 2021 - 10:38
Desc: Les chercheurs font rarement la une des journaux : l'annonce des prix Nobel, de rares manifestations, les polémiques de quelques grandes figures médiatiques, la réponse ciblée à une inquiétude suite à un phénomène de société, à cela se résume le plus souvent leur présence sur la scène médiatique. Que signifie être chercheur dans un contexte sociétal mouvant ? Quels sont les plaisirs et les difficultés de ce métier en pleine évolution ? En quoi consiste-t-il ? Comment et pourquoi devient-on chercheur ? Ce livre soulève ces quelques questions par le biais de témoignages de chercheurs d'horizons très divers, récemment recrutés au Centre National de la Recherche Scientifique (CNRS). L'initiative de ce livre est née à la suite de journées d'études axées sur les potentialités des itinéraires professionnels des chercheurs. Celles-ci ont mis en évidence de nombreux points communs malgré la diversité des parcours de « jeunes chercheurs » : des ressentis, des questions, des constats similaires, appuyés pourtant sur des expériences différentes. Les treize auteurs évoquent, au travers de leurs témoignages, toujours passionnés, parfois drôles, souvent émouvants, leurs « itinéraires » de chercheurs.
[hal-00760181] Advances in Human-Protein Interaction - Interactive and Immersive Molecular Simulations
Date: 14 jan 2021 - 11:29
Desc: [...]
[hal-00533099] Modeling the early stage of DNA sequence recognition within RecA nucleoprotein filaments.
Date: 14 jan 2021 - 11:29
Desc: Homologous recombination is a fundamental process enabling the repair of double-strand breaks with a high degree of fidelity. In prokaryotes, it is carried out by RecA nucleofilaments formed on single-stranded DNA (ssDNA). These filaments incorporate genomic sequences that are homologous to the ssDNA and exchange the homologous strands. Due to the highly dynamic character of this process and its rapid propagation along the filament, the sequence recognition and strand exchange mechanism remains unknown at the structural level. The recently published structure of the RecA/DNA filament active for recombination (Chen et al., Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structure, Nature 2008, 453, 489) provides a starting point for new exploration of the system. Here, we investigate the possible geometries of association of the early encounter complex between RecA/ssDNA filament and double-stranded DNA (dsDNA). Due to the huge size of the system and its dense packing, we use a reduced representation for protein and DNA together with state-of-the-art molecular modeling methods, including systematic docking and virtual reality simulations. The results indicate that it is possible for the double-stranded DNA to access the RecA-bound ssDNA while initially retaining its Watson-Crick pairing. They emphasize the importance of RecA L2 loop mobility for both recognition and strand exchange.
[hal-01688181] VLITL is a major cross-beta-sheet signal for fibrinogen A alpha-chain frameshift variants
Date: 14 jan 2021 - 11:28
Desc: The first case of hereditary fibrinogen A alpha-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 A alpha-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 A alpha-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'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 A alpha-chain peptide contained a motif (VLITL), with a high intrinsic propensity for beta-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-beta-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 A alpha-chain frameshift variants, yielding a previously unknown molecular basis for the pathogenesis of A alpha-chain amyloidosis.
Autres contacts
Institut de Biologie Physico-Chimique (IBPC)
13, rue Pierre et Marie Curie
75252 PARIS CEDEX 05
