Chris
CNRS research director
Adjunct professor of physics

Contact information
E-mail: chipot@illinois.edu
Phone: (217)-300-0380
Mailing address: 3165 Beckman Institute for Advanced
Science and Technology

405 North Mathews.
Urbana, Illinois 61801

Alternate address. Laboratoire international associé CNRS-UIUC. UMR 7565. Université de Lorraine. B.P. 70239. 54506 Vandœuvre-lès- Nancy, France

Web: http://www.lia-uiuc.cnrs.fr/


Education

- MS at Université Henri Poincaré, France.
- PhD at Université Henri Poincaré, France.
- Postdoctoral fellow at the Department of pharmaceutical chemistry, UCSF.
- Postdoctoral fellow at the NASA Ames Research Center.


Research areas

Development
Free-energy methods. We are interested in the exploratiFreeEnergyon of rare events in biology. Central to the scientific objectives of the Laboratoire International Associé is the development of novel computational approaches, which will allow high–performance simulations to explore biologically relevant, micro– to millisecond timescales, and be prepared for the exascale–computational era. The current simulation methodology spans timescales commonly ranging from pico– to microseconds. We aim at bridging the gap by means of methods at the confluence of importance– and enhanced–sampling algorithms. We are focusing on these two classes of methods, improving their ease of application to routine problems of biophysical relevance. In particular, we are facilitating the estimation of standard binding free energies, using a rigorous theoretical framework. Efficient construction of free-energy landscapes along chosen coarse variables is also being enhanced with the development of novel strategies, accelerating sampling of the relevant degrees of freedom with original algorithms.

Comer, J.; Gumbart, J. C.; Hénin, J.; Lelièvre, T.; Pohorille, A.; Chipot, C. The adaptive biasing force method: Everything you always wanted to know, but were afraid to ask. J. Phys. Chem. B 2015, 119, 1129-1151.
Fu, H.; Shao, X.; Chipot, C.; Cai, W. Extended adaptive biasing force algorithm. An on-the-fly implementation for accurate free-energy calculations. J. Chem. Theory Comput. 2016, 12, 3506-3513.


Kinetic modeling. Pm Concomitantly with the development of novel algorithms targeted at the exploration of rare events, we are reconciling thermodynamics and kinetics by means of Bayesian-inference schemes to build kinetic models underlying biological phenomena. Exploiting gradient-based free-energy calculations, our methodology supplies the position-dependent diffusivity, from whence mean first-passage times and rate constants can be inferred. This methodology has been recently extended to address anomalous diffusion, whereby the mean-squared displacement along the chosen coarse variable is no longer linear in time, turning to a fractional Smoluchowski description.

Comer, J.; Chipot, C.; González-Nilo, F. D. Calculating position-dependent diffusivity in biased molecular dynamics simulations. J. Chem. Theor. Comput. 2013, 9, 876-882.
Comer, J.; Schulten, K.; Chipot, C. Permeability of a fluid lipid bilayer to short-chain alcohols from first principles. J. Chem. Theory Comput. 2017, 13, 2523-2532.
Applications
Membrane proteins. AAC Membrane proteins are the gateways to the cell and to cellular compartments. In combination with their sophisticated environment, they perform a host of functions ranging from signal transduction, transport of metabolites to energy conversion. In mammals, up to 30% of the genome encodes membrane proteins, which today, represent the primary target for drug discovery. Yet, notwithstanding their significant population in the cell wall and their importance in cellular processes, membrane proteins are markedly less well characterized than hydrosoluble ones. This imbalance can be rationalized by the strong dependence of the structure and stability of membrane proteins on their native lipid environment. For many years, we have used molecular-dynamics simulations in synergy with experiment to dissect the interplay of membrane proteins with their surroundings, focusing on members of the mitochondrial carrier family, and on the p7 protein of Hepatitis C virus, crucial for assembly and release of infectious virions. In addition to addressing the dynamics of membrane proteins in near physiological conditions, we employ molecular dynamics simulations to rationalize the information gleaned in structural biophysics experiment in mimetic environments, notably in detergents.

Dehez, F.; Pebay-Peyroula, E.; Chipot, C. Binding of ADP in the mitochondrial ADP/ATP carrier is driven by an electrostatic funnel. J. Am. Chem. Soc. 2008, 130, 12725-12733.
Zoonens, M.; Masscheleyn, S.; Comer, J.; Pebay-Peyroula, E.; Chipot, C.; Miroux, B.; Dehez, F. Mitochondrial uncoupling protein 2 in dodecylphosphocholine: Partly denatured and severely inactivated. J. Am. Chem. Soc. 2013, 135, 15174-15182.

Molecular motors. ATPase Molecular motors are nanoscale devices, which harness the free energy from chemical reactions into mechanical work with minimal dissipation. Such motors serve an important purpose in living organisms, driving conformational transitions that regulate a variety of biological processes, from RNA translocation, ATP synthesis and hydrolysis, to cytoskeletal transport. Chemists have learned lessons taught by the cell machinery and the principles of energy transduction in biological motors to design and synthesize structurally simpler, yet functionally targeted abiological devices. These devices have found applications in various areas of molecular recognition, encompassing nanosensors and transducers, which, in turn, can be employed in an automated platform for the synthesis of small molecules, defining an area of frontier research that was awarded the Nobel Prize in Chemistry in 2016. Our research focuses on molecular motors at different scales, from small abiological, cyclodextrin-based nanodevices to the large biological complexes of the respiratory chain. Using molecular-dynamics simulations, our effort aims at reconciling structural, biochemical, thermodynamic and kinetic information to render a complete, detailed picture of the processes at play. In addition, we focus on the spurious mutations and oxidative stress that affects the efficiency of the respiratory complexes, in connection with a variety of mitochondrial diseases and aging.

Liu, P.; Shao, X.; Chipot, C.; Cai, W. The true nature of rotary movements in rotaxanes. Chem. Sci. 2016, 7, 457-462.
Singharoy, A.; Chipot, C.; Moradi, M.; Schulten, K. Chemomechanical coupling in hexameric protein- protein interfaces harnesses energy within V-Type ATPases. J. Am. Chem. Soc. 2017, 139, 293-310.

Publications:

Publications Database
  • Constant-pH molecular dynamics simulations for large biomolecular systems. Brian K Radak, Christophe Chipot, Donghyuk Suh, Sunhwan Jo, Wei Jiang, James C Phillips, Klaus Schulten, and Benoît Roux. Journal of Chemical Theory and Computation, 2017.
  • Tribute to Klaus Schulten. Emad Tajkhorshid and Christophe Chipot. Journal of Physical Chemistry B, 121:3203-3205, 2017.
  • Permeability of a fluid lipid bilayer to short-chain alcohols from first principles. Jeffrey Comer, Klaus Schulten, and Christophe Chipot. Journal of Chemical Theory and Computation, 13:2523-2532, 2017.
  • Chemomechanical coupling in hexameric protein-protein interfaces harnesses energy within V-type ATPases. Abhishek Singharoy, Christophe Chipot, Mahmoud Moradi, and Klaus Schulten. Journal of the American Chemical Society, 139:293-310, 2016.
  • Methodology for the simulation of molecular motors at different scales. Abhishek Singharoy and Christophe Chipot. Journal of Physical Chemistry B, 121:3502-3514, 2017.
  • Conserved methionine dictates substrate preference in Nramp-family divalent metal transporters. Aaron T. Bozzi, Lukas B. Bane, Wilhelm Weihofen, Anne McCabe, Abhishek Singharoy, Chris Chipot, Klaus Schulten, and Rachelle Gaudet. Proceedings of the National Academy of Sciences, USA, 113:10310-10315, 2016.
  • Molecular mechanism of processive 3' to 5' RNA translocation in the active subunit of the RNA exosome complex. Lela Vukovic, Christophe Chipot, Debora L. Makino, Elena Conti, and Klaus Schulten. Journal of the American Chemical Society, 138:4069-4078, 2016.
  • 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.
  • 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.
  • 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.
  • 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.