Some examples and selected publications
Exploring conformational spaces
With Frédéric Cazals (Inria Sophia-Antipolis), we have been interested in new ways of characterizing the potential energy landscape (PEL) defined on the conformational space of macromolecules, reasoning from incomplete (i.e., realistic) knowledge obtained through experimental data, modelling and simulations. This subject builds on earlier work based on more local descriptions of the PEL carried out with David Perahia (currently at ENS Cachan).
If proteins and nucleic acids are at the heart of Biology, their interactions are Biology. The problem of quantitatively understanding these interactions is similar to those of understanding their individual components, only squared. One phenomenological approach is to examine the structures and the behavior of individual components and that of their complexes when available. This has the advantage of looking at species on both sides of the chemical reaction: A + B —> A:B in order to appreciate the changes associated with complex formation.
This work was started as a collaboration with Joël Janin at Univ Paris-Sud Orsay and Pinak Chakrabarti at the Bose Institute in Kolkata, India, and has identified new physical-chemical features that may play a role in biological recognition.
Activation of a small G-protein, olfactory protein dynamics, hemoglobin
Simulations approaches have permitted a better understanding of the dynamics of individual proteins, such as Arf1, a small G protein involved in cellular traffic, and of the mechanism of binding small aromatic molecules to olfactory proteins, ...
... without, of course, forgetting hemoglobin, e.g.:
Modelling chromatin fibers
Some 20 years ago I particularly enjoyed modelling the chromatin 30 nm fiber in terms of the number of superhelical turns, DNA entry/exit angle on the nucleosome, linker lengths, helical twist of the DNA (in both nucleosome-bound and linker regions). This modelling played a central role in analyzing of some of the first AFM images (Leuba et al., 1994), and provided a basis for interpreting hydrodynamics data from the analytical ultracentrifuge (Robert, 1995). More and more relevant structural data has become available for such systems, which makes it tempting to return one day…