| Abstract
| - van der Waals force field parameters are difficult to determine from only experimental data because of theinsufficient data-to-parameter ratio, particularly for the diverse set of atom types necessary for force fieldsused in virtual ligand screening. We present a method which exploits the virtually unlimited number of abinitio calculations, as compared with experimental data, and does not have to rely on unphysical combinationrules used by most force fields. Interaction energies of all pairs of molecules from a set of eight compoundsat the MP2/d-aug-cc-pVDZ level with a counterpoise correction are used to simultaneously fit parameters ina buffered Lennard-Jones van der Waals potential for six atom types. The transferability of the parameters isdemonstrated 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 andthe van der Waals potential from the MMFF94 force field. Whereas, except for a few outliers, calculationsusing our van der Waals potential accurately reproduce the experimental values, the MMFF94 values aresystematically 30−40% too low. Finally, two possible effects contributing to the good agreement of thesublimation enthalpies calculated using our potential with experimental data are discussed: the increasedbasis set flexibility due to basis functions on adjacent bonded atoms and the systematic error resulting fromthe neglect of the intramolecular conformational energy in the calculation of the sublimation enthalpy.
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