Chris Chipot
CNRS research director, group leader


Contact:
Phone: +33 (0)3.83.68.40.97
Fax: +33 (0)3.83.68.43.87
E-mail:
 Christophe.Chipot@edam.uhp-nancy.fr
                                                                                    






 
 

Biographical sketch

Chris Chipot received his B.Sc. in physical chemistry from Nancy University, France. In 1990, he joined the Theoretical Chemistry group in Nancy, where he developed intermolecular potentials for the simulation of protein folding. In the course of his Ph.D. project sponsored by a Roussel-Uclaf fellowship, Chris Chipot was a visitor of the group of Harold A. Scheraga at Cornell University, and of Peter A. Kollman at the University of California in San Francisco, where he worked on electrostatics parametrization and free energy calculations, respectively. After he obtained in 1994 his Ph.D. with honors, cum laude, Chris Chipot joined the group of Peter A. Kollman, where he pursued his investigations on molecular recognition via free energy calculations. He was subsequently awarded a fellowship from the National Academy of Sciences, and joined in 1995 the group of Andrew Pohorille at the NASA Ames Research Center, where he worked on the folding of short peptides at aqueous interfaces. In 1996, he was appointed by the Centre National de la Recherche Scientifique research associate at the Theoretical Chemistry group in Nancy. He has been investigating eversince the interaction of proteins with membranes, using statistical mechanics, and develops new approaches for improving the description of intermolecular interactions in molecular simulations. He obtained his habilitation in 2000, was appointed research director in 2006 and currently heads the Equipe de Dynamique des Assemblages Membranaires. He has been the principal investigator of industrial contracts with Sanofi Aventis.


Honors and awards. In 1999, Chris Chipot was the recipient of a Young Researcher Award of the Société Française de Chimie for his work on protein folding at aqueous interfaces, and in 2001, of the bronze medal of the Centre National de la Recherche Scientifique.


Most cited publications.
  1. Chipot, C.; Jaffe, R.; Maigret, B.; Pearlman, D. A.; Kollman, P. A., Benzene dimer: A good model for π-π interactions in proteins? A comparison between the benzene and the toluene dimers in the gas phase and in an aqueous solution, J. Am. Chem. Soc. 1996, 118, 11217-11224 (171).
  2. Phillips, J. C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, L.; Schulten, K., Scalable molecular dynamics with NAMD, J. Comput. Chem. 2005, 26, 1781-1802 (101).
  3. Minoux, H.; Chipot, C., Cation-π interactions in proteins: Can simple models provide an accurate description ? J. Am. Chem. Soc. 1999, 121, 10366-10372 (75).











 Research areas


Transport phenomena across the biological membranes
Given the available three-dimensional structure of channels and transporters, we are interested in the underlying mechanisms whereby these membrane proteins fulfill their cellular function, assisting the translocation of chemical species across the cell wall. Employing free energy calculations, we determine the energetics characterizing these transport processes, while dissecting at the atomic level the intricate relationship between structure and function. Among the membrane proteins investigated in the group are the glycerol transport facilitator (GlpF) and the mitochondrial ADP/ATP carrier (AAC).





Protein-membrane interactions
Many essential life processes are performed by proteins and protein assemblies embedded in, or bound to the surface of membranes. Biological membranes provide a highly dynamic and complex microenvironment, offering intimate proximity between polar and non-polar media, which is conducive to the organization of biologically relevant molecules. In the light of molecular dynamics simulations, we decipher the complex mechanisms whereby peptides pertaining to the Hepatitics C RNA-replication machinery anchor into the lipid bilayer, or at the surface thereof. Using the same tools, we investigate the interaction of nanotubes formed of stacked cyclic peptides with the membrane.





Polarizable force fields
Pairwise 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. cation- π interactions.





Free energy methods
Determination 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.























Publications

  1. Chipot, C.; Maigret, B.; Rivail, J. L.; Scheraga, H. A., Modeling amino acid side chains. 1. Determination of net atomic charges from ab initio self-consistent field molecular electrostatic properties, J. Phys. Chem. 1992, 96, 10276-10284.
  2. Chipot, C.; Rinaldi, D.; Rivail, J. L., Intramolecular electron correlation in the self-consistent reaction field model of solvation. A MP2/6-31G** ab initio study of the NH3-HCl complex, Chem. Phys. Lett. 1992, 191, 287-292.
  3. Chipot, C.; Ángyán, J. G.; Ferenczy, G. G.; Scheraga, H. A., Transferable net atomic charges from distributed multipole analysis for the description of electrostatic properties. A case study of saturated hydrocarbons, J. Phys. Chem. 1993, 97, 6628-6636.
  4. Chipot, C.; Ángyán, J. G.; Maigret, B.; Scheraga, H. A., Modeling amino acid side chains. 2. Determination of point charges from electrostatic properties. Towards transferable point charge models, J. Phys. Chem. 1993, 97, 9788-9796.
  5. Chipot, C.; Ángyán, J. G.; Maigret, B.; Scheraga, H. A., Modeling amino acid side chains. 3. Influence of intra- and intermolecular environment on point charges, J. Phys. Chem. 1993, 97, 9797-9807.
  6. Ángyán, J. G.; Chipot, C., A comprehensive approach to molecular charge density models: From distributed multipoles to fitted atomic charges, Int. J. Quantum Chem. 1994, 52, 17-37.
  7. Chipot, C.; Millot, C.; Maigret, B.; Kollman, P. A., Molecular dynamics free energy perturbation calculations. Influence of nonbonded parameters on the free energy of hydration of charged and neutral species, J. Phys. Chem. 1994, 98, 11362-11372.
  8. Chipot, C.; Gorb, L. G.; Rivail, J. L., Proton transfer in the mono-, di- and trihydrated complexes of HF and HCl. A MP2/6-31+G** ab initio study in the self-consistent reaction field model of solvation, J. Phys. Chem. 1994, 98, 1601-1607.
  9. Chipot, C.; Millot, C.; Maigret, B.; Kollman, P. A., Molecular dynamics free energy perturbation calculations. Influence of nonbonded parameters on the free energy of hydration of charged and neutral species, J. Phys. Chem. 1994, 98, 11362-11372.
  10. Chipot, C.; Millot, C.; Maigret, B.; Kollman, P. A., Molecular dynamics free energy perturbation calculations. Influence of the truncation of long-range nonbonded interactions on the free energy of hydration of polar species, J. Chem. Phys. 1994, 101, 7953-7962.
  11. Rivail, J. L.; Antonczak, S.; Chipot, C.; Ruiz-Lopez, M. F.; Gorb, L. Water-assisted reactions in solution. in Structure and Reactivity in Aqueous Solution: Characterization of Chemical and Biological Systems, Cramer, C. J.; Truhlar, D. G., Eds., ACS Symposium Series No. 568. ACS, Washington D. C., 1994, ch. 11, pp. 154-167.
  12. Chipot, C.; Maigret, B.; Pearlman, D. A. Alternative approaches to potential of mean force calculations: Free energy perturbation versus thermodynamic integration. The case study of hydrophobic interactions. in E. C. C. C. 1 Computational Chemistry, AIP Conference Proceedings 330, Bernardi, F.; Rivail, J. L., Eds. American Institute of Physics, New York, 1995, pp. 287-294.
  13. Chipot, C.; Jaffe, R.; Maigret, B.; Pearlman, D. A.; Kollman, P. A., Benzene dimer: A good model for π-π interactions in proteins? A comparison between the benzene and the toluene dimers in the gas phase and in an aqueous solution, J. Am. Chem. Soc. 1996, 118, 11217-11224.
  14. Chipot, C.; Kollman, P. A.; Pearlman, D. A., Alternative approaches to potential of mean force calculations: Free energy perturbation versus thermodynamic integration. Case study of some representative nonpolar interactions, J. Comput. Chem. 1996, 17, 1112-1131.
  15. Chipot, C.; Maigret, B.; Pearlman, D. A.; Kollman, P. A., Molecular dynamics potential of mean force calculations: A study of the toluene-ammonium π π-cation interactions, J. Am. Chem. Soc. 1996, 118, 2998-3005.
  16. Pohorille, A.; Chipot, C.; New, M.; Wilson, M. A. Molecular modeling of protocellular functions. in Pacific Symposium on Biocomputing '96, Hunter, L.; Klein, T. E., Eds.World Scientific, Singapore, 1996, pp. 550-569.
  17. Chipot, C.; Pohorille, A., Structure and dynamics of small peptides at aqueous interfaces. A multi-nanosecond molecular dynamics study., J. Mol. Struct./Theochem 1997, 398/399, 529-535.
  18. Chipot, C.; Wilson, M. A.; Pohorille, A., Interactions of anesthetics with the water-hexane interface. A molecular dynamics study, J. Phys. Chem. B 1997, 101, 782-791.
  19. Kollman, P.; Dixon, R.; Cornell, W.; Fox, T.; Chipot, C.; Pohorille, A. The development/application of a minimalist force field using a combination of ab initio and experimental data. in Computer simulation of biomolecular systems: Theoretical and experimental applications, Van Gunsteren, W. F.; Weiner, P. K., Eds. Escom, The Netherlands, 1997, pp. 83-96.
  20. Pohorille, A.; Wilson, M. A.; Chipot, C., Interaction of alcohols and anesthetics with the water-hexane interface. A molecular dynamics study, Progr. Colloid Polym. Sci. 1997, 103, 29-40.
  21. Soetens, J. C.; Millot, C.; Chipot, C.; Jansen, G.; Ángyán, J. G.; Maigret, B., Effect of polarizability on the calculation of potential of mean force. The guanidinium-guanidinium ion pair in water, J. Phys. Chem. B 1997, 101, 10910-10917.
  22. Chipot, C.; Ángyán, J. G.; Millot, C., Statistical analysis of distributed multipoles derived from the molecular electrostatic potential, Mol. Phys. 1998, 94, 881-895.
  23. Chipot, C.; Pohorille, A., Conformational equilibria of terminally blocked single amino acids at the water-hexane interface. A molecular dynamics study, J. Phys. Chem. B 1998, 102, 281-290.
  24. Chipot, C.; Pohorille, A., Folding and translocation of the undecamer of poly-L-leucine across the water-hexane interface. A multi-nanosecond molecular dynamics study, J. Am. Chem. Soc. 1998, 120, 11912-11924.
  25. Cornell, W. D.; Chipot, C. Alternative approaches to charge distribution calculations. in Encyclopedia of computational chemistry, Schleyer, P. v. R.; Allinger, N. L.; Clark, T.; Gasteiger, J.; Kollman, P. A.; Schaefer III, H. F.; Schreiner, P. R., Eds., vol. 1. Wiley and Sons, Chichester, 1998, pp. 258-263.
  26. Pohorille, A.; Wilson, M.A.; New, M.H.; Chipot, C., Concentrations of anesthetics across the water-membrane interface; The Meyer-Overton hypothesis revisited, Toxicology Lett. 1998, 100, 421-430.
  27. Chipot, C.; Maigret, B.; Pohorille, A., Early events in the folding of an amphipathic peptide. A multi-nanosecond molecular dynamics study, Proteins: Structure, Function and Genetics 1999, 36, 383-399.
  28. Minoux, H.; Chipot, C., Cation-π interactions in proteins: Can simple models provide an accurate description ?, J. Am. Chem. Soc. 1999, 121, 10366-10372.
  29. Pohorille, A.; Wilson, M. A.; Schweighofer, K.; New, M. H.; Chipot, C. Interactions of membranes with small molecules and peptides. in Theoretical and Computational Chemistry - Computational Molecular Biology, Leszczynski, J., Ed., vol. 8. Elsevier, The Netherlands, 1999, pp. 485-535.
  30. Rogalska, E.; Rogalski, M.; Gulik-Krzywicki, T.; Gulik, A.; Chipot, C., Self-assembly of chlorophenols in water, Proc. Natl. Acad. Sci. USA 1999, 96, 6577-6580.
  31. Stofer, E.; Chipot, C.; Lavery, R., Free energy calculations of Watson-Crick base pairing in aqueous solution, J. Am. Chem. Soc. 1999, 121, 9503-9508.
  32. Celebi, N.; Ángyán, J. G.; Dehez, F.; Millot, C.; Chipot, C., Distributed polarizabilities derived from induction energies: A finite perturbation approach, J. Chem. Phys. 2000, 112, 2709-2717.
  33. Chipot, C.; Luque, F. J., Fast evaluation of induction energies: A second-order perturbation theory approach, Chem. Phys. Lett. 2000, 332, 190-198.
  34. Couturier, R.; Chipot, C., Parallel molecular dynamics using OpenMP on a shared memory machine, Comp. Phys. Comm. 2000, 124, 49-59.
  35. Dehez, F.; Soetens, J. C.; Chipot, C.; Ángyán, J. G.; Millot, C., Determination of distributed polarizabilities from a statistical analysis of induction energies, J. Phys. Chem. A 2000, 104, 1293-1303.
  36. Minoux, H.; Chipot, C.; Brown, D.; Maigret, B., Structure of barbourin, the only αIIb β3-specific disintegrin, J. Comput. Aided Molec. Design 2000, 14, 317-327.
  37. Rozanska, X.; Chipot, C., Modeling ion-ion interaction in proteins: A molecular dynamics free energy calculation of the guanidinium-acetate association, J. Chem. Phys. 2000, 112, 9691-9694.
  38. Chipot, C., Insights into the self-assembly of small, organic molecules: Case study of 2,4,6-trichlorophenol, J. Phys. Chem. B 2001, 105, 5987-5993.
  39. Chipot, C.; Dehez, F.; Ángyán, J. G.; Millot, C.; Orozco, M.; Luque, F. J., Alternative approaches for the calculation of induction energies. Characterization, effectiveness and pitfalls, J. Phys. Chem. A 2001, 105, 11505-11514.
  40. Dehez, F.; Chipot, C.; Millot, C.; Ángyán, J. G., Fast and accurate determination of induction energies: Reduction of topologically distributed polarizability models, Chem. Phys. Lett. 2001, 338, 180-188.
  41. Dixit, S. B.; Chipot, C., Can absolute free energies of association be estimated from molecular mechanical simulations ? The biotin-streptavidin system revisited, J. Phys. Chem. A 2001, 105, 9795-9799.
  42. Bas, D.; Dorison-Duval, D.; Moreau, S.; Bruneau, P.; Chipot, C., Rational determination of transfer free energies of small drugs across the water-oil interface, J. Med. Chem. 2002, 45, 151-159.
  43. Chipot, C.; Pearlman, D. A., Free energy calculations. The long and winding gilded road, Mol. Sim. 2002, 28, 1-12.
  44. Ángyán, J. G.; Chipot, C.; Dehez, F.; H0Š1ttig, C.; Jansen, G.; Millot, C., OPEP: A tool for the optimal partitioning of electric properties, J. Comput. Chem. 2003, 24, 997-1008.
  45. Chipot, C., Rational determination of charge distributions for free energy calculations, J. Comput. Chem. 2003, 24, 409-415.
  46. Collet, O.; Chipot, C., Non-Arrhenius behavior in the unfolding of a short, hydrophobic α-helix. Complementarity of molecular dynamics and lattice model simulations, J. Am. Chem. Soc. 2003, 125, 6573-6580.
  47. Pohorille, A.; Wilson, M. A.; Chipot, C., Membrane peptides and their role in protobiological evolution, Orig. Life and Evol. Biosph. 2003, 33, 173-197.
  48. Tarek, M.; Maigret, B.; Chipot, C., Molecular dynamics investigation of an oriented cyclic peptide nanotube in DMPC bilayers, Biophys. J. 2003, 85, 2287-2298.
  49. Hénin, J.; Chipot, C., Overcoming free energy barriers using unconstrained molecular dynamics simulations, J. Chem. Phys. 2004, 121, 2904-2914.
  50. Treptow,W. L.; Chipot, C.; Maigret, B.; Tarek, M., Coupled motions between pore and voltage-sensor domains: A model for Shaker B, a voltage-gated potassium channel, Biophys. J. 2004, 87, 2365-2379.
  51. Chipot, C. Free energy calculations in biological systems. How useful are they in practice? in New algorithms for macromolecular simulation, Leimkuhler, B.; Chipot, C.; Elber, R.; Laaksonen, A.; Mark, A. E.; Schlick, T.; Schütte, C.; Skeel, R., Eds., vol. 49. Springer Verlag, Berlin, 2005, pp. 183-209.
  52. Chipot, C.; Hénin, J., Exploring the free energy landscape of a short peptide using an average force, J. Chem. Phys. 2005, 123, 244906.
  53. Chipot, C.; Ángyán, J. G., Continuing challenges in the parametrization of intermolecular force fields. Towards an accurate description of electrostatic and induction terms, New J. Chem. 2005, 29, 411-420.
  54. Chipot, C.; Rozanska, X.; Dixit, S. B., Can free energy calculations be fast and accurate at the same time? Binding of low-affinity, non-peptide inhibitors to the SH2 domain of the src protein, J. Comput. Aided Mol. Des. 2005, 19, 765-770.
  55. Hénin, J.; Pohorille, A.; Chipot, C., Insights into the recognition and association of transmembrane α-helices. The free energy of α-helix dimerization in glycophorin A, J. Am. Chem. Soc. 2005, 127, 8478-8484.
  56. Phillips, J. C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, L.; Schulten, K., Scalable molecular dynamics with NAMD, J. Comput. Chem. 2005, 26, 1781-1802.
  57. Chipot, C.; Klein, M. L.; Tarek, M. Modeling lipid membranes. in The handbook of materials modeling. Methods and models of materials modeling, Catlow, R.; Shercliff, H.; Yip, S., Eds., vol. 1. Kluwer Academic Publishers, Dordrecht, 2005, pp. 929-958.
  58. Hénin, J.; Maigret, B.; Tarek, M.; Escrieut, C.; Fourmy, D.; Chipot, C., Probing a model of a GPCR/ligand complex in an explicit membrane environment. The human cholecystokinin-1 receptor, Biophys. J. 2006, 90, 1232-1240.
  59. Sapay, N.; Montserret, R.; Chipot, C.; Brass, V.; Moradpour, D.; Deléage, G.; Penin, F., NMR structure and molecular dynamics of the in-plane membrane anchor domain of nonstructural protein 5A from bovine viral diarrhea virus, Biochemistry 2006, 45, 2221-2233.
  60. Yu, Y. M.; Cai, W. S.; Chipot, C.; Shao, X. G., Molecular dynamics study of the inclusion of cholesterol into cyclodextrins, J. Phys. Chem. B 2006, 110, 6372-6378.
  61. Chipot, C. La dynamique moléculaire. Observer la matičre en mouvement. in Les Nanosciences: Nanotechnologies et nanophysique, Lahmani, M.; Houdy, P., Eds., vol. 3. Belin, Paris, 2006.
  62. Chipot, C.; Tarek, M., Interaction of a peptide nanotube with a water-membrane interface, Phys. Biol. 2006, 3, S20-S25.
  63. Hénin, J.; Chipot, C., Insights into the interaction of lipid membranes with cholesterol at high concentration, Chem. Phys. Lett. 2006, 425, 329-335.
  64. Hénin, J.; Schulten, K.; Chipot, C., Conformational equilibrium in alanine-rich peptides probed by reversible stretching simulations, J. Phys. Chem. B 2006, 110, 16718-16723.
  65. Chipot, C.; Pohorille, A. Calculating free energy differences from perturbation theory. in Free energy calculations. Theory and applications in chemistry and biology, Chipot, C.; Pohorille, A., Eds. Springer Verlag, Berlin-Heidelberg, 2007.
  66. Dehez, F.; Tarek, M.; Chipot, C., Energetics of ion transport in a  peptide nanotube, J. Phys. Chem. B. 200, 111, 10633-10635.
  67. Chipot, C.; Schulten, K. Understanding the structure and the function of membrane proteins using free energy calculations. in Biophysical approaches of structure and functions of membrane proteins, Pebay-Peyroula, E., Ed. Wiley and sons, New York, 2007.
  68. Chipot, C. Free energy calculations applied to membrane proteins. in Molecular modeling of proteins, Kukol, A., Ed. The Humana Press, 2007.
  69. Dehez, F.; Ángyán, J. G.; Soteras Gutiérrez, I.; Luque, F. J.; Schulten, K.; Chipot, C. Modeling induction phenomena in intermolecular interactions with an ab initio force field, J. Chem. Theor. Comput. 2007, 3, 1914-1926.
  70. Soteras Gutiérrez, I.; Curutchet, C.; Bidon-Chanal, A.; Dehez, F.;. Ángyán, J. G.; Orozco, M.;Chipot, C.; Luque, F. J. Derivation of distributed models of atomic polarizability for molecular simulations, J. Chem. Theor. Comput. 2007, 3, 1901-1913.
  71. Hénin, J.; Tajkhorshid, E.; Schulten, K.; Chipot, C., Diffusion of glycerol through Escherichia coli aquaglyceroporin GlpF, Biophys. J. 2008, 94, 832-839.
  72. Yu, Y.; Cai, W.; Chipot, C.; Sun, T.; Shao, X., Spatial arrangement of α-cyclodextrins in a rotaxane. Insights from free-energy calculations,  J. Phys. Chem. B 2008 (in press). 
  73. Cai, W.; Sun, T.; Shao, X.; Chipot, C. Can the anomalous aqueous solubility of β-cyclodextrin be explained by its hydration free energy alone? Phys. Chem. Chem. Phys. 2008 (in press).










Collaborations

Dr. János G.Ángyán
Laboratoire de Cristallographie et de Modélisation des Matériaux Minéraux et Biologiques
Nancy Université, France

 Professor Eva Pebay-Peyroula
Institut de Biologie Structurale
Grenoble, France

 Dr. François Penin
Institut de Biologie et Chimie des Protéines
Lyon, France

 Professor Klaus Schulten
Theoretical and Computational Biophysics Group
University of Illinois at Urbana-Champaign, USA

Professor Javier Luque
Facultat de Farmacía
Universitat de Barcelona, Spain

Professor Andrew Pohorille
Biomolecular and Cellular Modeling Program
NASA Ames Research Center, USA

Professors Cai Wensheng and Shao Xueguang
Department of Chemistry
Nankai University, China










Outreach


Lecture notes        Les méthodes numériques de la dynamique moléculaire

 		Numerical methods for molecular dynamics

 		Métodos numéricos en dinámica molecular



Books                

Free Energy Calculations: Theory and Applications in Chemistry and Biology .
(Springer Series in Chemical Physics).

C. Chipot and A. Pohorille, editors.

Springer-Verlag, Berlin and Heidelberg.
    

New Algorithms for Macromolecular Simulation.
(Lecture Notes in Computational Science & Engineering).

Leimkuhler, B.; Chipot, C.; Elber, R.; Laaksonen, A.; Mark, A.; Schlick, T.; Schütte, C.; Skeel, R. editors.

Springer-Verlag, Berlin and Heidelberg.          










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