2010 H. Julian Allen Award Winners – Eric Darve and Andrew Pohorille

Eric Darve and Andrew Pohorille, “Calculating Free Energies Using Average Force,” Journal of Chemical Physics 115 (November 22, 2001) 9169-9183.

Abstract:

How do proteins fold into their native three-dimensional structures, enzymes interact with candidate drugs, proteins in muscles stretch in response to the applied force or channels mediate permeation of ions and nutrients across cell walls? A common feature of these, and many other important problems in chemistry and molecular biology, is that one needs to know how the free energy of the system changes during the process. Our award winning 2001 paper published in the Journal of Chemical Physics provides a general solution to this problem. We derive formulas for calculating statistically averaged forces acting on the system along arbitrary coordinates that describe chemical or biological processes of interest. Then, we give a prescription how these forces can be rapidly adjusted in an adaptive manner such that, on average, there is no force acting on the system along the selected reaction coordinates. Without sacrifice of theoretical rigor, this guarantees uniform sampling of all relevant states of the system, which in turn implies optimal efficiency of free energy calculations. The method is being used by a rapidly increasing number of researchers, always yielding significant improvements in efficiency and accuracy.

Biographies:

Andrew Pohorille received Ph.D. in theoretical physics and structural biology from University of Warsaw. He did his postdoctoral work at the institut de Biologie Physico-Chimique in Paris under Prof. Bernard Pullman.

Since 1992 he has been professor of Chemistry and Pharmaceutical Chemistry at the University of California San Francisco. In 1996 he joined the staff of NASA Ames Research Center. In 2002 he was awarded NASA Exceptional Scientific Achievement Medal. His main interests have been focused on modeling the origins of life, computer simulations of biomolecular systems, modeling genetic and metabolic networks, and statistical mechanics of condensed phases.

Eric Darve received Ph.D. in Applied Mathematics from Pierre et Marie Curie University in Paris under Prof. Olivier Pironneau. Between 1999 and 2001, he held a postdoctoral position in the Center of Turbulence Research at Stanford and at NASA Ames, working with Andrew Pohorille. Since then he has been a faculty member at the Department of Mechanical Engineering at Stanford. His research is focused on the development of numerical methods for large scale scientific computing with applications in biomolecular simulations, fluid and solid mechanics, and electromagnetics.