MERCK MOLECULAR-FORCE FIELD .2. MMFF94 VAN-DER-WAALS AND ELECTROSTATIC PARAMETERS FOR INTERMOLECULAR INTERACTIONS

This article defines the parameterization and performance of MMFF94 fo r intermolecular interactions. It specifies the novel ''buffered'' fun ctional forms used for treating van der Waals (vdW) and electrostatic interactions, and describes the use of: (1) high quality ab initio dat a to parameterize vdW interactions involving aliphatic hydrogens; and (2) HF/6-31G calculations on hydrogen-bonded complexes to parameteriz e nonbonded interactions in polar systems. Comparisons show that appro priate trends in the HF/6-31G data are well reproduced by MMFF94 and that intermolecular interaction energies and geometries closely parall el those given by the highly regarded OPLS force field. A proper balan ce between solvent-solvent, solvent-solute, and solute-solute interact ions, critically important for prospective success in aqueous simulati ons, thus appears to be attained. Comparison of MMFF94, OPLS, CHELPG e lectrostatic potential fit, QEq, Gasteiger, and Abraham charges for 20 small molecules and ions also shows the close correspondence between MMFF94 and OPLS. As do OPLS and all current, widely used force fields, MMFF94 employs ''effective pair potentials'' which incorporate in an averaged way the increases in polarity which occur in high dielectric media. Some limitations of this approach are discussed and suggestions for possible enhancements to MMFF94's functional form are noted. (C) 1996 by John Wiley & Sons, Inc.