MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular-interactionenergies and geometries

This article provides extensive comparisons for the MMFF94, MMFF94s, CFF95, CVFF, MSI CHARMm, AMBER*, OPLS", MM2*, and MM3* force fields to experiment al and high-quality ab initio data for conformational energies and to scale d ab initio data for hydrogen-bonded complexes. Some comparisons are also p resented for CHARMM 22. The tests of conformational energies consisted of t wo sets of comparisons to experiment and one more extensive set of comparis ons to relatively high-quality nb initio data. As in the derivation of MMFF 94, scaled HF/6-31G* energies and geometries were used to assess the reason ableness of the calculated intermolecular interaction energies and geometri es. The comparisons for intermolecular interactions arrear to be the first broadly based comparisons to appear in the chemical literature. Taken toget her, the comparisons reveal that most of the force fields make sizable erro rs and frequently produce qualitatively incorrect results for both conforma tional and intermolecular-interaction energies. For example, three of the f orce fields produce individual errors in conformational energy of more than 10 kcal/mol, and four rate thiophene as a stronger hydrogen-bond acceptor than ammonia. Only MMFF94 and MMFF94s perform consistently well. Some MMFF deficiencies are apparent, however, particularly for conformational energie s of halocyclohexanes. These deficiencies, and others recently found for co ndensed-phase simulations, will need to be addressed in any future reparame terization of MMFF. The quantum-chemical data used in this work have been p laced on the Computational Chemistry List web site. (C) 1999 John Wiley & S ons, Inc. J Comput Chem 20: 730-748, 1999.