Lennard-Jones parameters for the combined QM/MM method using the B3LYP/6-31+G*/AMBER potential

A combined DFT quantum mechanical and AMBER molecular mechanical potential (QM/MM) is presented for use in molecular modeling and molecular simulations of large biological systems. In our approach we evaluate Lennard-Jones parameters describing the interaction between the quantum mechanical (QM) part of a System, which is described at the B3LYP/6-31+G* level of theory, and the molecular mechanical (MM) part of the system, described by the AMBER force field. The Lennard-Jones parameters for this potential are obtained by calculating hydrogen bond energies and hydrogen bond geometries for a large set of bimolecular systems. in which one hydrogen bond monomer is described quantum mechanically and the other is treated molecular mechanically. We have investigated more than I (X) different bimolecular systems, finding very good agreement between hydrogen bond energies and geometries obtained from the combined QM/MM calculations and results obtained at the QM level of theory, especially with respect to geometry. Therefore, based on the Lennard-Jones parameters obtained in our study, we anticipate that the B3LYP/631+G*/AMBER potential will be a precise tool to explore intermolecular interactions inside a protein environment, (c) 2005 Wiley Periodicals, Inc.