National Center for Design of
Biomimetic Nanoconductors
Benoit Roux
Contact:
Benoit Roux is Professor in the department of Pediatrics, Biochemistry & Molecular Biology at the University of Chicago. His research interests include computational studies of ion channels at multiple time scales.
Research
Projects in the Roux group are designed to address fundamental issues about ion permeation and extend our understanding of channel function using a combination of computational (molecular dynamics, free energy simulations, umbrella sampling, Poisson-Boltzmann calculations, ab initio calculations) and experimental approaches (bilayer experiments, x-ray crystallography). They will address specific issues concerning ion stability, ion-ion interactions, and selectivity present in narrow pores, using the KcsA channel (wild-type and mutants) as a model system to carry out theoretical studies. They intend to determine the structure of specific mutants of KcsA that are of particular interest using x-ray crystallography and Molecular Replacement method and compare with the results from MD simulations. They will also address a number of issues concerning the importance of electrostatic effects, macromolecular geometry and pore shape, ionic screening, on valence specificity and access resistance in the case of wide aqueous vestibules. The group will determine the cation and anion distribution in OmpF porin using ion substitution and x-ray crystallography difference map techniques. Finally, the group will also address general issues concerning the structure of inhibitors in complex with K+ channels as well as their mode of action and contribute to the on-going efforts aimed at elucidating the structure and gating mechanism in channels on the basis of a wide range of experimental data using computational models of the KcsA, KvAP, Shaker.
All of the ion channel work of the Roux lab is strongly relevant to the mission of the Center. Center interactions will be most strongly focused on polarizable force fields and Brownian dynamics, but it is expected that the Center will benefit from Roux' participation in every aspect of the computational work. Roux has already done Brownian dynamics simulations of alpha-hemolysin---that work will be a foundation to start very strongly on validation of methods against the experimental results from the Bayley lab.
Related Publications
Allen, T W, O S Andersen, and B Roux (2003). The structure of gramicidin A in a lipid bilayer environment determined using molecular dynamics simulations and solid-state NMR data. J. Am. Chem. Soc., 125:9868–9877.
W. Im, S. Seefeld, and B. Roux, A Grand Canonical Monte Carlo-Brownian Dynamics Algorithm for Simulating Ion Channels, Biophysical Journal, Vol. 79, No. 2, pp. 788-801, 2000.
Im, W. and B. Roux (2001). Brownian Dynamics Solutions of Ions Channels: A General Treatment of Electrostatic Reaction Fields for Molecular Pores of Arbitrary Geometry. J. Chem. Phys., 115:4850–4861.
Im, W and B Roux (2002). Ion Permeation and Selectivity of OmpF Porin: A Theoretical Study Based on Molecular Dynamics, Brownian Dynamics, and Continuum Electrodiffusion Theory. J Mol Biol, 322:851–869.
Lamoureux, G., A.D. MacKerell, and B. Roux (2003). A simple water model with Drude-oscillator polarizability. J Chem Phys, 119:5185–5197.
Lamoureux, G. and B. Roux (2003). Modelling induced polarizability with Drude oscillators: Theory and molecular dynamics simulation algorithm. J Chem Phys, 119:3025–3039.
Noskov S.Y., Beneche S. and B. Roux 2004. Control of ion selectivity in potassiuim channels by electrostatic and dynamic properties of carbonyl ligands. Nature 431:830
B. Roux, “Theoretical and computational models of ion channels,” Current Opinion in Structural Biology, Vol. 12, pp. 182-189, 2002.
B. Roux and S. Berneche, “On the Potential Functions used in Molecular Dynamics Simulations of Ion Channels,” Biophysical Journal, Vol. 82, No. 3, pp. 1681-1684, 2002.