Grid methods for free energy calculations and ligand scoring

COMP 237

Viktor Hornak, viktor.hornak@sunysb.edu1, Raphaël Geney2, Robert C. Rizzo, rizzorc@gmail.com3, and Carlos L Simmerling, carlos.simmerling@sunysb.edu2. (1) Center for Structural Biology, Stony Brook University, Stony Brook, NY 11794, (2) Department of Chemistry, SUNY Stony Brook, Stony Brook, NY 11794, (3) Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794-3600
A variant of one-window free energy grid (OWFEG) method for protein-ligand interaction is evaluated. Current implementation uses implicit solvation model to significantly increase computational efficiency and improve sampling. Several scoring schemes based on interpolation of free energy grids are suggested and evaluated in terms of correctness of rank ordering a series of ligands with respect to experimental binding data. The influence of implicit (several variants of Generalized Born model) and explicit solvation models on the quality of ligand ranking is investigated. The reproducibility of results related to the choice of “reference” compound is also examined. Lastly, computational efficiency with regard to solvation model is discussed and contrasted to other standard methods for free energy calculations, such as MM-PBSA.
 

Poster Session
6:00 PM-8:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Computers in Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006