Semiempirical calculations of binding enthalpy for protein-ligand complexes

A systematic semiempirical quantum mechanical study of the interactions between proteins and ligands has been performed to determine the ability of this approach for the accurate estimation of the enthalpic contribution to the binding free energy of the protein-ligand systems. This approach has been applied for eight test protein-ligand complexes with experimentally known binding enthalpies. The calculations were performed using the semiempirical PM3 approach incorporated in the MOPAC 97, ZAVA originally elaborated in Algodign, and MOPAC 2002 with MOZYME facility packages. Special attention was paid to take into account structural water molecules, which were located in the protein-ligand binding site. It was shown that the results of binding enthalpy calculations fit experimental data within similar to2 kcal/ mol in the presented approach. (C) 2003 Wiley Periodicals; Inc.