New methods for efficient direct calculation of ligand binding free energies

AEI 50

Michael R. Shirts, michael.shirts@columbia.edu1, John D. Chodera, jchodera@gmail.com2, and Richard Friesner1. (1) Department of Chemistry, Columbia University, New York, NY 10027, (2) Department of Chemistry, Stanford University, Clark Center, MC 5447, Stanford, CA 94305-5447
We present two methodological developments for computation of ligand binding free energies. The first is a maximum-likelihood method for combination of equilibrium simulations at different thermodynamic states, which is similar to the weighted histogram analysis method (WHAM), but removes the need for discretization of the energy into histograms. It additionally gives a direct estimate for the uncertainty, and is expected to be applicable for a wide range of chemical simulations. The second is a configuration bias method for free energy computation of ligand binding in implicit solvent, greatly saving the time required for side chain rearrangement. We demonstrate how these methods can be applied to free energy computations of ligand binding of FKBP-12 with several ligands.
 

Academic Employment Initiative
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Academic Employment Initiative

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007