How to improve docking accuracy of AutoDock4.2: a case study using different electrostatic potentials.

Molecular docking, which is the indispensable emphasis in predicting binding conformations and energies of ligands to receptors, constructs the high-throughput virtual screening available. So far, increasingly numerous molecular docking programs have been released, and among them, AutoDock 4.2 is a widely used docking program with exceptional accuracy. It has heretofore been substantiated that the calculation of partial charge is very fundamental for the accurate conformation search and binding energy estimation. However, no systematic comparison of the significances of electrostatic potentials on docking accuracy of AutoDock 4.2 has been determined. In this paper, nine different charge-assigning methods, including AM1-BCC, Del-Re, formal, Gasteiger-Hückel, Gasteiger-Marsili, Hückel, Merck molecular force field (MMFF), and Pullman, as well as the ab initio Hartree-Fock charge, were sufficiently explored for their molecular docking performance by using AutoDock4.2. The results clearly demonstrated that the empirical Gasteiger-Hückel charge is the most applicable in virtual screening for large database; meanwhile, the semiempirical AM1-BCC charge is practicable in lead compound optimization as well as accurate virtual screening for small databases.