- Professor, Department of Biochemistry and Molecular Biophysics, Department of Pediatrics, Institute of Molecular Pediatric Sciences, Committee on Cancer Biology
Ph.D. Harvard University, 1990
M.Sc. University of Montreal, 1984
B.Sc. University of Montreal, 1981
The University of Chicago
929 East 57th Street
Chicago, IL 60637
Phone: (773) 834-3557
Theoretical and Computational Studies of the Structure, Dynamics and Function of 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 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.