Development of Polarizable Models for Molecular Mechanical Calculations. 4. van der Waals Parametrization

In the previous publications of this series, we presented a set of Thole induced dipole interaction models using four types of screening functions. In this work, we document our effort to refine the van der Waals parameters for the Thole polarizable models. Following the philosophy of AMBER force field development, the van der Waals (vdW) parameters were tuned for the Thole model with linear screening function to reproduce both the <i>ab initio</i> interaction energies and the experimental densities of pure liquids. An in-house genetic algorithm was applied to maximize the fitness of “chromosomes” which is a function of the root-mean-square errors (RMSE) of interaction energy and liquid density. To efficiently explore the vdW parameter space, a novel approach was developed to estimate the liquid densities for a given vdW parameter set using the mean residue–residue interaction energies through interpolation/extrapolation. This approach allowed the costly molecular dynamics simulations be performed at the end of each optimization cycle only and eliminated the simulations during the cycle. Test results show notable improvements over the original AMBER FF99 vdW parameter set, as indicated by the reduction in errors of the calculated pure liquid densities (<i>d</i>), heats of vaporization (<i>H</i><sub>vap</sub>), and hydration energies. The average percent error (APE) of the densities of 59 pure liquids was reduced from 5.33 to 2.97%; the RMSE of <i>H</i><sub>vap</sub> was reduced from 1.98 to 1.38 kcal/mol; the RMSE of solvation free energies of 15 compounds was reduced from 1.56 to 1.38 kcal/mol. For the interaction energies of 1639 dimers, the overall performance of the optimized vdW set is slightly better than the original FF99 vdW set (RMSE of 1.56 versus 1.63 kcal/mol). The optimized vdW parameter set was also evaluated for the exponential screening function used in the Amoeba force field to assess its applicability for different types of screening functions. Encouragingly, comparable performance was observed when the optimized vdW set was combined with the Thole Amoeba-like polarizable model, particularly for the interaction energy and liquid density calculations. Thus, the optimized vdW set is applicable to both types of Thole models with either linear or Amoeba-like screening functions.