Docking with combined use of a force field and a quantum-chemical method

Abstract

The paper presents the results concerning the application of docking programs FLM to combined use of the MMFF94 force field and the semiempirical quantum-chemical method PM7 in the docking procedure. At the first step of this procedure a fairly wide range of low-energy minima of the protein-ligand complex is found in the frame of the MMFF94 force field using the FLM program. The energies of all these minima are recalculated using the PM7 method and the COSMO solvent continuum model at the second step. On the basis of these calculations the deepest minimum of the protein-ligand energy, calculated by the PM7 method with COSMO solvent, is determined, which gives the position of the ligand closest to its position in the crystal of the protein-ligand complex. It is shown that the first step of the combined procedure is performed more quickly and more efficiently in vacuum, rather than with a solvent model.