Importance of accurate charges in molecular docking: quantum mechanical/molecular mechanical (QM/MM) approach.

ABSTRACT: The extent to which accuracy of electric charges plays a role in protein-ligand docking is investigated through development of a docking algorithm, which incorporates quantum mechanical/molecular mechanical (QM/MM) calculations. In this algorithm, fixed charges of ligands obtained from force field parameterization are replaced by QM/MM calculations in the protein environment, treating only the ligands as the quantum region. The algorithm is tested on a set of 40 cocrystallized structures taken from the Protein Data Bank (PDB) and provides strong evidence that use of nonfixed charges is important. An algorithm, dubbed "Survival of the Fittest" (SOF) algorithm, is implemented to incorporate QM/MM charge calculations without any prior knowledge of native structures of the complexes. Using an

SUBMITTER: Cho AE 

PROVIDER: S-EPMC3920598 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature