Structural Dynamics of Macromolecules - Marc DELARUE

Activities of the Unit

We seek to understand at the molecular level the structure, function and dynamics of some biological nanomachines involved in the fundamental processes of life. To this end, we use a combination of experimental (e.g. X-Ray crystallography) and computational tools.

-The first class of molecules concern DNA metabolism and cancer, namely DNA polymerases and topoisomerases. We especially focus on polymerases involved in double-strand break repair system. Because these nanomachines undergo large movements during their catalytic cycle, we study the likely pathway between the different forms by coarse-grained newly developed methods.

-The second class of molecules that we study are membrane proteins that are members of the pentameric ligand-gated ion channels family. Here electrostatic effects are especially important as the gating process itself is driven by pH; to understand these effects we develop new methods. This work is done in collaboration with P.J. Corringer group in Institut Pasteur (molecular biology, biochemistry, electrophysiology).

We also study the gating transition by molecular dynamics simulations in collaboration with Marc Baaden (IBPC, CNRS)

 Unit website
  Bacterial pentameric pH-gated cys-loop receptor in its membrane environment
Coarse-grained model of citrate synthase using the Elastic Network

The three
most significative publications  :

1. Nury, H., Van Renterghem, C., Weng, Y., Tran, A., Baaden, M., Dufresne, V., Changeux, J.-P., Sonner, J.-M., Delarue, M. and Corringer, P.-J. (2011) X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nature, 469, 428-431.
2. Romain, F., Barbosa, I., Gouge, J., Rougeon, F. and Delarue, M. (2009) Conferring a template-dependent polymerase activity to terminal deoxynucleotidyltransferase by mutations in the Loop1 region. Nucleic Acids Res., 37, 4642-4656.
3. Koehl, P., Orland, H. and Delarue, M. (2009) Beyond the Poisson-Boltzmann model: modeling biomolecule-water and water-water interactions. Phys. Rev. Lett., 102, (8):087801. Epub 2009 Feb 24.