Evaluating Force-Field London Dispersion Coefficients Using the Exchange-Hole Dipole Moment Model

London
dispersion interactions play an integral role in materials
science and biophysics. Force fields for atomistic molecular simulations
typically represent dispersion interactions by the 12-6 Lennard-Jones
potential using empirically determined parameters. These parameters
are generally underdetermined, and there is no straightforward way
to test if they are physically realistic. Alternatively, the exchange-hole
dipole moment (XDM) model from density-functional theory predicts
atomic and molecular London dispersion coefficients from first principles,
providing an innovative strategy to validate the dispersion terms
of molecular-mechanical force fields. In this work, the XDM model
was used to obtain the London dispersion coefficients of 88 organic
molecules relevant to biochemistry and pharmaceutical chemistry and
the values compared with those derived from the Lennard-Jones parameters
of the CGenFF, GAFF, OPLS, and Drude polarizable force fields. The
molecular dispersion coefficients for the CGenFF, GAFF, and OPLS models
are systematically higher than the XDM-calculated values by a factor
of roughly 1.5, likely due to neglect of higher order dispersion terms
and premature truncation of the dispersion-energy summation. The XDM
dispersion coefficients span a large range for some molecular-mechanical
atom types, suggesting an unrecognized source of error in force-field
models, which assume that atoms of the same type have the same dispersion
interactions. Agreement with the XDM dispersion coefficients is even
poorer for the Drude polarizable force field. Popular water models
were also examined, and TIP3P was found to have dispersion coefficients
similar to the experimental and XDM references, although other models
employ anomalously high values. Finally, XDM-derived dispersion coefficients
were used to parametrize molecular-mechanical force fields for five
liquidsbenzene, toluene, cyclohexane, n-pentane,
and n-hexanewhich resulted in improved accuracy
in the computed enthalpies of vaporization despite only having to
evaluate a much smaller section of the parameter space.