Improved scoring of ligand-protein interactions using OWFEG free energy grids.

摘要

A new approach to rapidly score protein-ligand interactions is tested on several protein-ligand systems. Results using this approach - the OWFEG free energy grid - are quite promising and are generally in better agreement with experiment (in some cases much better) than those obtained employing scoring techniques currently in wide use. The OWFEG free energy grid is generated from a one-window free energy perturbation MD simulation (Pearlman, D. A. J. Med. Chem. 1999, 42, 4313-4324). The OWFEG approach is applied to three protein systems: IMPDH, MAP kinase p38, and HIV-1 aspartyl protease. OWFEG scores are compared to experimental K(i) and IC50 data in each case. Empirical scoring functions applied to the same systems for comparison include ChemScore, Piecewise Linear Potential (PLP), and Dock energy score.