Research

Charles Robert

Some examples and selected publications

Under construction

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).

Roth CA, Dreyfus T, Robert* CH, Cazals* F .  In Press.   Hybridizing Rapidly Exploring Random Trees and Basin Hopping Yields an Improved Exploration of Energy Landscapes. J Comput Chem.
Cazals F, Roth A, Dreyfus T, Mazauric D, Robert CH .  2015.   Conformational ensembles and sampled landscapes: analysis and comparison. J. Comp. Chem.. 36:1213-31.
Batista PR, Pandey G, Bisch PM, Pascutti PG, Perahia* D, Robert* CH .  2011.   Free energy profiles along consensus normal modes provide insight into HIV-1 protease flap opening. J. Chem. Theor. Comput.. 7:2348-52.

Protein-protein interactions

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.

Chakravarty D, Janin J, Robert CH, Chakrabarti P .  2015.   Changes in protein structure at the interface accompanying complex formation.. IUCrJ. 2:643–652.
Boyer B, Ezelin J, Poulain P, Saladin A, Zacharias M, Robert CH, Prévost C .  2015.   An integrative approach to the study of filamentous oligomeric assemblies, with application to RecA.. PLoS One. 10:e0116414.
Laurin Y., Savarin P., Robert CH, Takahashi M., Eyer J., Prevost C., Sacquin-Mora S. .  2015.   Investigating the Structural Variability and Binding Modes of the Glioma Targeting NFL-TBS.40-63 Peptide on Tubulin. Biochemistry. 54:3660–3669.
Guharoy M, Janin J, Robert CH .  2010.   Side-chain rotamer transitions at protein-protein interfaces. PROTEINS: Structure, Function, and Bioinformatics. 78:3219–25.

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, ...

Ben Hamida–Rebaï M, Robert CH .  2010.   A computational study of a recreated G protein-GEF reaction intermediate competent for nucleotide exchange: fate of the Mg ion. PLoS ONE. 5:e9142.
Hajjar E, Perahia D, Débat H, Nespoulous C, Robert CH.  2006.  Odorant Binding and Conformational Dynamics in the Odorant-binding Protein. J Biol Chem. 281:29929–29937.

... without, of course, forgetting hemoglobin, e.g.:

Robert CH, Gill SJ, Wyman J.  1988.  Quantitative analysis of linkage in macromolecules when one ligand is present in limited total quantity. Biochemistry. 27:6829–6835.

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…

Robert CH.  1995.  Estimating friction coefficients of mixed globular/chain molecules, such as protein/DNA complexes. Biophys J. 69:840–848.
Leuba S.H, Yang G., Robert CH, Samori B., van Holde K., Zlatanova J., Bustamante C..  1994.  Three-dimensional structure of extended chromatin fibers as revealed by tapping-mode scanning force microscopy. Proc Natl Acad Sci U S A. 91:11621–11625.