Merck molecular force field. V. Extension of MMFF94 using experimental data, additional computational data, and empirical rules

This article describes the extension of the Merck Molecular Force Field (MMFF94) to a much broader range of organic systems. It also describes a preliminary parameterization of MMFF94 for the hydronium and hydroxide ions and for various halide, alkalai, and alkalai earth ions as well as for such “protein” metals as Zn2+, Ca2+, Cu2+, Cu+, Fe2+, and Fe3+. The extension employed computational data on charge distributions, molecular geometries, and conformational energies for a series of oxysulfur (particularly sulfonamide) and oxyphosphorous compounds and for a diverse set of small molecules and ions not covered in the core parameterization. It also employed experimental data for approximately 2800 good-quality structures extracted from the Cambridge Structural Database (CSD). Some of the additional computational data were used to extend the explicit parameterization of electrostatic interactions and to more widely define a useful additive approximation for the “bond polarity” parameters (bond charge increments) used in MMFF94. Both the experimental and computational data served to define reference bond lengths and angles that the extended force field uses in conjunction with force constants obtained from carefully calibrated empirical rules. The extended torsion parameters consist partly of explicit parameters derived to reproduce MP2/6-31G* conformational energies and partly of “default parameters” provided by empirical rules patterned after those used in DREIDING and UFF but calibrated, where possible, against computationally derived MMFF94 torsion parameters. Comparisons to experimental data show that MMFF94 reproduces crystallographic bond lengths and bond angles with relatively modest root mean square (rms) deviations of approx. 0.02 Å and 2°, respectively. © John Wiley & Sons, Inc.