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-04548404] Molecular Origin of Distinct Hydration Dynamics in Double Helical DNA and RNA Sequences
Date: 16 avr 2024 - 15:17
Desc: [...]
[hal-03011659] Electrostatically-driven fast association and perdeuteration allow detection of transferred cross-relaxation for G protein-coupled receptor ligands with equilibrium dissociation constants in the high-to-low nanomolar range.
Date: 18 nov 2020 - 11:14
Desc: The mechanism of signal transduction mediated by G protein-coupled receptors is a subject of intense research in pharmacological and structural biology. Ligand association to the receptor constitutes a critical event in the activation process. Solution-state NMR can be amenable to high-resolution structure determination of agonist molecules in their receptor-bound state by detecting dipolar interactions in a transferred mode, even with equilibrium dissociation constants below the micromolar range. This is possible in the case of an inherent ultra-fast diffusive association of charged ligands onto a highly charged extracellular surface, and by slowing down the (1)H-(1)H cross-relaxation by perdeuterating the receptor. Here, we demonstrate this for two fatty acid molecules in interaction with the leukotriene BLT2 receptor, for which both ligands display a submicromolar affinity.
[hal-01498056] Lipid concentration and molar ratio boundaries for the use of isotropic bicelles.
Date: 29 Mar 2017 - 17:04
Desc: Bicelles are model membranes generally made of long-chain dimyristoylphosphatidylcholine (DMPC) and short-chain dihexanoyl-PC (DHPC). They are extensively used in the study of membrane interactions and structure determination of membrane-associated peptides, since their composition and morphology mimic the widespread PC-rich natural eukaryotic membranes. At low DMPC/DHPC (q) molar ratios, fast-tumbling bicelles are formed in which the DMPC bilayer is stabilized by DHPC molecules in the high-curvature rim region. Experimental constraints imposed by techniques such as circular dichroism, dynamic light scattering, or microscopy may require the use of bicelles at high dilutions. Studies have shown that such conditions induce the formation of small aggregates and alter the lipid-to-detergent ratio of the bicelle assemblies. The objectives of this work were to determine the exact composition of those DMPC/DHPC isotropic bicelles and study the lipid miscibility. This was done using (31)P nuclear magnetic resonance (NMR) and exploring a wide range of lipid concentrations (2-400 mM) and q ratios (0.15-2). Our data demonstrate how dilution modifies the actual DMPC/DHPC molar ratio in the bicelles. Care must be taken for samples with a total lipid concentration <=250 mM and especially at q ~ 1.5-2, since moderate dilutions could lead to the formation of large and slow-tumbling lipid structures that could hinder the use of solution NMR methods, circular dichroism or dynamic light scattering studies. Our results, supported by infrared spectroscopy and molecular dynamics simulations, also show that phospholipids in bicelles are largely segregated only when q > 1. Boundaries are presented within which control of the bicelles\textquoteright q ratio is possible. This work, thus, intends to guide the choice of q ratio and total phospholipid concentration when using isotropic bicelles.
[hal-00760127] Understanding small biomolecule-biomaterial interactions: A review of fundamental theoretical and experimental approaches for biomolecule interactions with inorganic surfaces.
Date: 3 déc 2012 - 15:03
Desc: Interactions between biomolecules and inorganic surfaces play an important role in natural environments and in industry, including a wide variety of conditions: marine environment, ship hulls (fouling), water treatment, heat exchange, membrane separation, soils, mineral particles at the earth's surface, hospitals (hygiene), art and buildings (degradation and biocorrosion), paper industry (fouling) and more. To better control the first steps leading to adsorption of a biomolecule on an inorganic surface, it is mandatory to understand the adsorption mechanisms of biomolecules of several sizes at the atomic scale, that is, the nature of the chemical interaction between the biomolecule and the surface and the resulting biomolecule conformations once adsorbed at the surface. This remains a challenging and unsolved problem. Here, we review the state of art in experimental and theoretical approaches. We focus on metallic biomaterial surfaces such as TiO(2) and stainless steel, mentioning some remarkable results on hydroxyapatite. Experimental techniques include atomic force microscopy, surface plasmon resonance, quartz crystal microbalance, X-ray photoelectron spectroscopy, fluorescence microscopy, polarization modulation infrared reflection absorption spectroscopy, sum frequency generation and time of flight secondary ion mass spectroscopy. Theoretical models range from detailed quantum mechanical representations to classical forcefield-based approaches. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
[halshs-02424173] Itinéraires Bis
Date: 26 déc 2019 - 18:47
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.
Autres contacts
Institut de Biologie Physico-Chimique (IBPC)
13, rue Pierre et Marie Curie
75252 PARIS CEDEX 05