|Mailing address:||3047 Beckman Institute of Advanced Science and Technology |
|405 North Mathews
Urbana, Illinois 61801
CNRS research director
Laboratoire international associé CNRS-UIUC. UMR 7565. Université de Lorraine. B.P. 70239. 54506 Vandœuvre-lès- Nancy, France
M.Sc at Université Henri Poincaré, France.
Ph.D. at Université Henri Poincaré, France.
Postdoctoral fellow at the Department of pharmaceutical chemistry, UCSF.
Postdoctoral fellow at the NASA Ames Research Center.
of free energy differences can follow three possible routes: (i)
Estimation from probability distributions, (ii) direct computation, and
(iii) evaluation of the free energy derivative over some order
parameter and its subsequent integration. We are focusing on the latter
two classes of methods, improving their ease of application to routine
problems of biophysical relevance. In particular, we are facilitating
the design of site-directed mutagenesis experiments within the
framework of free energy perturbation. Efficient construction of free
energy profiles along a chosen order parameter, ideally a reaction
coordinate, is also being enhanced in the development of novel
strategies relying on the evaluation of the free energy derivative and
the continuous estimate of the biasing force required to overcome the
free energy barriers.
|Transport phenomena across membranes|
GlpF, the facilitator of glycerol transport belongs to a family of membrane
proteins, the aquaporins, investigated by Peter Agre, 2003 Nobel prize winner
in chemistry. Employing free-energy calculations along a model reaction
coordinate, we have followed the diffusion of a glycerol molecule in the
channel of GlpF and shown that, on the one hand, transport and, on the other
hand, isomerization and reorientation, span comparable time scales. A kinetic
model suggests that glycerol diffusion appears as a slow process only on
account of the many failed attempts of the permeant to cross the selectivity
translocon guides proteins that are generated by the ribosome. We have
established that it offers an environment intermediate between water
and membrane, hence reducing the energetic cost for translocating
charged amino acids and the gain for the passage of highly hydrophobic
side chains. We have further confirmed that while the behavior of the
nascent chain in the translocon is similar to that in bulk water, the
bottleneck located in the midst of the channel favors entropically
self-organization of secondary structures
additive potential energy functions utilized for the simulation of
biological systems rely on an implicit and, hence, incomplete treatment
of electronic polarization. However effective for a wide range of
applications, these force fields rapidly reach their limitations when
induction phenomena are significant. To address this issue, an approach
has been devised, relying on the derivation of distributed
polarizabilities from induction energy maps determined quantum
mechanically. The resulting models of implicitly interacting atomic
polarizabilities are now being incorporated into potential energy
functions and probed in geometry optimization calculations, e.g.
Diffusive models of membrane permeation with explicit orientational freedom.
Jeffrey Comer, Klaus Schulten, and Christophe Chipot. Journal of Chemical Theory and Computation, 10:2710-2718, 2014. (DNA P41).
Calculation of lipid-bilayer permeabilities using an average force.
Jeffrey Comer, Klaus Schulten, and Christophe Chipot. Journal of Chemical Theory and Computation, 10:554-564, 2014. (DNA P41).
Molecular basis of drug resistance in A/H1N1 virus.
Ariela Vergara-Jaque, Horacio Poblete, Eric Lee, Klaus Schulten, Fernando González-Nilo, and Christophe Chipot. Journal of Chemical Information and Modeling, 52:2650-2656, 2012. (DNA P41).
The p7 protein of hepatitis C virus forms structurally plastic, minimalist ion channels.
Danielle E. Chandler, Francois Penin, Klaus Schulten, and Christophe Chipot. PLoS Computational Biology, 8:e1002702, 2012. (10 pages).
Recognition of methylated DNA through methyl-CpG binding domain proteins.
Xueqing Zou, Wen Ma, Ilia Solov'yov, Christophe Chipot, and Klaus Schulten. Nucleic Acids Research, 40:2747-2758, 2012.
Free energy of nascent-chain folding in the translocon.
James Gumbart, Christophe Chipot, and Klaus Schulten. Journal of the American Chemical Society, 133:7602-7607, 2011.
Free-energy cost for translocon-assisted insertion of membrane proteins.
James Gumbart, Christophe Chipot, and Klaus Schulten. Proceedings of the National Academy of Sciences, USA, 108:3596-3601, 2011.
Oligomerization state of photosynthetic core complexes is correlated with the dimerization affinity of a transmembrane helix.
Jen Hsin, Loren LaPointe, Alla Kazy, Christophe Chipot, Alessandro Senes, and Klaus Schulten. Journal of the American Chemical Society, 133:14071-14081, 2011.
Cytoplasmic domain filter function in the mechanosensitive channel of small conductance.
Ramya Gamini, Marcos Sotomayor, Christophe Chipot, and Klaus Schulten. Biophysical Journal, 101:80-89, 2011.
A glycophorin A-like framework for the dimerization of photosynthetic core complexes.
Jen Hsin, Chris Chipot, and Klaus Schulten. Journal of the American Chemical Society, 131:17096-17098, 2009.
Membrane curvature induced by aggregates of LH2s and monomeric LH1s.
Danielle E. Chandler, James Gumbart, John D. Stack, Christophe Chipot, and Klaus Schulten. Biophysical Journal, 97:2978-2984, 2009.
Understanding structure and function of membrane proteins using free energy calculations.
Christophe Chipot and Klaus Schulten. In Eva Pebay-Peyroula, editor, Biophysical analysis of membrane proteins. Investigating structure and function, pp. 187-211. Wiley, Weinheim, 2008.
Diffusion of glycerol through Escherichia coli aquaglyceroporin GlpF.
Jerome Henin, Emad Tajkhorshid, Klaus Schulten, and Christophe Chipot. Biophysical Journal, 94:832-839, 2008.
Modeling induction phenomena in intermolecular interactions with an ab initio force field.
Francois Dehez, Janos G. Angyan, Ignacio Soteras Gutierrez, F. Javier Luque, Klaus Schulten, and Christophe Chipot. Journal of Chemical Theory and Computation, 3:1914-1926, 2007.
Conformational equilibrium in alanine-rich peptides probed by reversible stretching simulations.
Jerome Henin, Klaus Schulten, and Christophe Chipot. Journal of Physical Chemistry B, 110:16718-16723, 2006.
Scalable molecular dynamics with NAMD.
James C. Phillips, Rosemary Braun, Wei Wang, James Gumbart, Emad Tajkhorshid, Elizabeth Villa, Christophe Chipot, Robert D. Skeel, Laxmikant Kale, and Klaus Schulten. Journal of Computational Chemistry, 26:1781-1802, 2005.