Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions

TLDR

MMFF94, like other widely used force fields, uses effective pair potentials that average polarity increases in high‑dielectric media. This article defines the parameterization and performance of MMFF94 for intermolecular interactions. It introduces buffered functional forms for van der Waals and electrostatic interactions, parameterized with high‑quality ab initio data for aliphatic hydrogens and HF/6‑31G* calculations for hydrogen‑bonded complexes, and discusses limitations and possible enhancements. Comparisons show MMFF94 reproduces HF/6‑31G* trends and yields interaction energies and geometries comparable to OPLS, achieves a balanced solvent–solvent, solvent–solute, and solute–solute interaction model, and closely matches OPLS charge schemes for 20 small molecules and ions. © 1996 John Wiley & Sons, Inc.

Abstract

This article defines the parameterization and performance of MMFF94 for intermolecular interactions. It specifies the novel “buffered” functional forms used for treating van der Waals (vdW) and electrostatic interactions, and describes the use of : (1) high quality ab initio data to parameterize vdW interactions involving aliphatic hydrogens; and (2) HF/6-31G* calculations on hydrogen-bonded complexes to parameterize nonbonded interactions in polar systems. Comparisons show that appropriate trends in the HF/6-31G* data are well reproduced by MMFF94 and that intermolecular interaction energies and geometries closely parallel those given by the highly regarded OPLS force field. A proper balance between solvent–solvent, solvent–solute, and solute–solute interactions, critically important for prospective success in aqueous simulations, thus appears to be attained. Comparison of MMFF94, OPLS, CHELPG electrostatic 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. © 1996 John Wiley & Sons, Inc.