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

Summary: Direct Derivation of van der Waals Force Field Parameters from Quantum Mechanical
Interaction Energies
A. J. Bordner,* C. N. Cavasotto, and R. A. Abagyan
The Scripps Research Institute, 10550 North Torrey Pines Rd., Mail TPC-28, San Diego, California 92037
ReceiVed: January 21, 2003; In Final Form: May 23, 2003
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 correction are used to simultaneously fit parameters in
a buffered Lennard-Jones 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.


Source: Abagyan, Ruben - School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego


Collections: Biology and Medicine