End-point free energy calculations: Synergy from continuum solvent and molecular dynamics methods

COMP 106

Jessica M. J. Swanson, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92037-0365 and J. Andrew McCammon, Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Mail Code 0365, La Jolla, CA 92093-0365.
A thorough investigation of end-point free energy calculations will be presented. These methods combine gas phase energies from explicit solvent simulations with continuum solvation energies to evaluate the free energy of the bound and free states of a binding reaction. This work highlights several important areas: the association free energy, arising from one molecule's loss of translational and rotational freedom upon binding; the conformational free energy, due to both molecules' change in conformational freedom; and compatibility between implicit and explicit solvent models. Direct calculations of the association and conformational free energies from a molecular dynamics simulation will be discussed. The performance of several commonly used Poisson Boltzmann continuum parameter sets will be compared, and a new set of radii for use with AMBER partial charges will be presented. A number of insights from this investigation can be applied in more computationally efficient scoring and rescoring methods.

Docking and Scoring
1:30 PM-4:50 PM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- 109B, Oral

Division of Computers in Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004