Direct Derivation of van der Waals Force Field Parameters from Quantum Mechanical Interaction Energies

摘要

van der Waals force field parameters are difficult to determine from only experimental data because of the insufficient data-to-parameter ratio, particularly for the diverse set of atom types necessary for force fields used in virtual ligand screening. We present a method which exploits the virtually unlimited number of ab initio calculations, as compared with experimental data, and does not have to rely on unphysical combination rules used by most force fields. Interaction energies of all pairs of molecules from a set of eight compounds at the MP2/d-aug-cc-pVDZ level with a counterpoise correlation are used to simultaneously fit parameters in a buffered Lennard-Jonews van der Waals potential for six atom types. The transferability of the parameters is demonstrated by the reproducibility of ab initio dimer energies for four molecules in a validation set. Next, sublimation energies of 14 alkanes and 11 nonalkane compounds are calculated using both our potential and the van der Waals potential from the MMFF94 force field. Whereas, except for a few outliers, calculations using our van der Waals potential accurately reproduce the experimental values, the MMFF94 values are systematically 30-40% too low. Finally, two possible effects contributing to the good agreement of the sublimation enthalpies calculated using our potential with experimental data are discussed: the increased basis set flexibility due to basis functions on adjacent bonded atoms and the systematic error resulting from the neglect of the intramolecular conformational energy in the calculation of the sublimation enthalpy.