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-01926896] Applications to water transport systems: general discussion
Date: 19 Nov 2018 - 15:00
Desc: no abstract
[hal-02306930] Involvement of the cysteine-rich head domain in activation and desensitization of the P2X1 receptor
Date: 7 Oct 2019 - 11:48
Desc: P2X receptors (P2XRs) are ligand-gated ion channels activated by extracellular ATP. Although the crystal structure of the zebrafish P2X4R has been solved, the exact mode of ATP binding and the conformational changes governing channel opening and desensitization remain unknown. Here, we used voltage clamp fluorometry to investigate movements in the cysteine-rich head domain of the rat P2X1R (A118-I125) that projects over the proposed ATP binding site. On substitution with cysteine residues, six of these residues (N120-I125) were specifically labeled by tetramethyl-rhodamine-maleimide and showed significant changes in the emission of the fluorescence probe on application of the agonists ATP and benzoyl-benzoyl-ATP. Mutants N120C and G123C showed fast fluorescence decreases with similar kinetics as the current increases. In contrast, mutants P121C and I125C showed slow fluorescence increases that seemed to correlate with the current decline during desensitization. Mutant E122C showed a slow fluorescence increase and fast decrease with ATP and benzoyl-benzoyl-ATP, respectively. Application of the competitive antagonist 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) resulted in large fluorescence changes with the N120C, E122C, and G123C mutants and minor or no changes with the other mutants. Likewise, TNP-ATP-induced changes in control mutants distant from the proposed ATP binding site were comparably small or absent. Combined with molecular modeling studies, our data confirm the proposed ATP binding site and provide evidence that ATP orients in its binding site with the ribose moiety facing the solution. We also conclude that P2XR activation and desensitization involve movements of the cysteine-rich head domain.
[hal-02370038] The modelling and enhancement of water hydrodynamics: general discussion
Date: 19 Nov 2019 - 11:50
Desc: no abstract
[hal-01926768] Structure and function of natural proteins for water transport: general discussion
Date: 19 Nov 2018 - 14:27
Desc: An abstract was not provided in the original work, so a preliminary abstract has been prepared as follows. The discussion focused on the structure and function of natural proteins for water transport and examined, among other things, Finkelstein's model of the movement of water molecules. It was discussed that these water molecules move as a unit with a coefficient of friction proportional to the number of molecules, but do not allow electroosmotic transport in the opposite direction of water flow because of their narrow width. The entropy of water molecules entering the nanotubes has also been discussed. There is evidence that entropy increases for certain tube sizes and water distances. The group discussed that the activation barrier can only be determined by measuring the permeabilities at different temperatures, with the pores of carbon nanotubes having the highest water permeability and thus the lowest activation energy, which is even lower than the best of the aquaporins.
[hal-01926861] Biomimetic water channels: general discussion
Date: 19 Nov 2018 - 14:56
Desc: An abstract was not provided in the original work, so a preliminary abstract has been prepared as follows. Of the various topics discussed, a few are briefly mentioned below. A focus on biomimetic water channels concerned the formation of G4 quartet hydrogels. It was found that these hydrogels can form with several different monovalent cations (Li+, Na+, K+, Rb+, and NH4+), but not well with Cs+. The cations are separated from each other in the central channel by about 3.5 Angstroms. The location of anions in G4-potassium complexes or G4 complexes with any cations was also discussed, since the presence of anions affects column stack formation and ionic conductivity. The issue of selectivity for use in environmental remediation was briefly addressed. I4 quartet channels were also an important topic of discussion.
Autres contacts
Institut de Biologie Physico-Chimique (IBPC)
13, rue Pierre et Marie Curie
75252 PARIS CEDEX 05
