Benoit Roux
Research Summary / Selected Publications
We use theoretical and computational methods to advance our understanding of the structure, dynamics and function of biological macromolecular systems at the atomic level.
We are particularly interested in issues concerning the function of ion channels and other membrane transport proteins such as ion permeation, ion selectivity, and gating. Most of our work on ion channels is computational though we have recently started to add an experimental component to our research with electrophysiological measurements and protein crystallography.
The computational approach called "molecular dynamics" (MD) is central to our work. It consists of constructing detailed atomic models of the macromolecular system and, having described the microscopic forces with a potential function, using Newton's classical equation, F=MA, to literally "simulate" the dynamical motions of all the atoms as a function of time. The calculated trajectory, though an approximation to the real world, provides detailed information about the time course of the atomic motions, which is nearly impossible to access experimentally. We use such all-atom MD simulations to rigorously compute conformational free energies, and binding free energies.
In addition, other computational approaches, at different level of complexity and sophistication, can be very useful. In particular, Poisson Boltzmann (PB) continuum electrostatic models, in which the influence of the solvent is incorporated implicitly, plays an increasingly important role in estimating the solvation free energy of macromolecular assemblies. We are also spending efforts in the development of new computational approaches (polarizable force field, solvent boundary potentials, efficient sampling methods) for studying biological macromolecular systems.
We use theoretical and computational methods to advance our understanding of the structure, dynamics and function of biological macromolecular systems at the atomic level.
We are particularly interested in issues concerning the function of ion channels and other membrane transport proteins such as ion permeation, ion selectivity, and gating. Most of our work on ion channels is computational though we have recently started to add an experimental component to our research with electrophysiological measurements and protein crystallography.
The computational approach called "molecular dynamics" (MD) is central to our work. It consists of constructing detailed atomic models of the macromolecular system and, having described the microscopic forces with a potential function, using Newton's classical equation, F=MA, to literally "simulate" the dynamical motions of all the atoms as a function of time. The calculated trajectory, though an approximation to the real world, provides detailed information about the time course of the atomic motions, which is nearly impossible to access experimentally. We use such all-atom MD simulations to rigorously compute conformational free energies, and binding...
S. Berneche and B. Roux, "Energetics of Ion Conduction through the K+ Channel", Nature 414, 73-77 (2001).
S.Y. Noskov, S. Berneche and B. Roux, "Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands", Nature 431, 830-834 (2004).
H. Yu, S.Y. Noskov, and B. Roux. Two mechanisms of ion selectivity in protein binding sites. Proc. Natl. Acad. Sci. USA 107, 20329-20334 (2010).
H. Yu, I.M. Ratheal, P. Artigas, and B. Roux. Protonation of key acidic residues is critical for the K-selectivity of the Na/K pump. Nat. Struct. Mol. Biol. 18, 1159-63 (2011).
B. Chanda, O. K. Asamoah, R. Blunck, B. Roux, F. Bezanilla. "Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement", Nature 436, 852-856 (2005).
A.Y. Lau and B. Roux. The hidden energetics of ligand binding and activation in a glutamate receptor. Nat. Struct. Mol. Biol. 18 283-287 (2011).
F. Khalili-Araghi, V. Jogini, V. Yarov-Yarovoy, E. Tajkhorshid, B. Roux, and K. Schulten. Calculation of the gating charge for the Kv1.2 voltage-activated potassium channel. Biophys. J. 98, 2189-2198 (2010).
S. Yang, L. Blachowicz, L. Makowski, and B. Roux. Multidomain assembled states of Hck tyrosine kinase in solution. Proc. Natl. Acad. Sci. USA 107, 15757-15762 (2010).
Y. Deng and B. Roux. Computations of Standard Binding Free Energies with Molecular Dynamics Simulations. J. Phys. Chem. B 113, 2234–2246 (2009).
B. Dhakshnamoorthy, S. Raychaudhury, L. Blachowicz, and B. Roux. Cation-selective Pathway of OmpF Porin Revealed by Anomalous X-ray Diffraction. J Mol. Biol. 396, 293-300 (2010).
B.K. Ziervogel and B. Roux. The Binding of Antibiotics in OmpF Porin. Structure 21, 76-87 (2013).
Y.L. Lin, Y. Meng, W. Jiang, and B. Roux. Explaining why Gleevec is a specific and potent inhibitor of Abl kinase. Proc. Natl. Acad. Sci. USA 110, 1664-1669 (2013).
S. Berneche and B. Roux, "Energetics of Ion Conduction through the K+ Channel", Nature 414, 73-77 (2001).
S.Y. Noskov, S. Berneche and B. Roux, "Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands", Nature 431, 830-834 (2004).
H. Yu, S.Y. Noskov, and B. Roux. Two mechanisms of ion selectivity in protein binding sites. Proc. Natl. Acad. Sci. USA 107, 20329-20334 (2010).
H. Yu, I.M. Ratheal, P. Artigas, and B. Roux. Protonation of key acidic residues is critical for the K-selectivity of the Na/K pump. Nat. Struct. Mol. Biol. 18, 1159-63 (2011).
B. Chanda, O. K. Asamoah, R. Blunck, B. Roux, F. Bezanilla. "Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement", Nature 436, 852-856 (2005).
