Improving Generalized Born Models by Exploiting Connections to Polarizable Continuum Models. I. An Improved Effective Coulomb Operator.

Abstract

We investigate the generalized Born (GB) implicit solvation model in comparison with polarizable continuum models (PCMs). We show that the GB model is intimately connected to the conductor-like PCM (C-PCM), a method that is accurate for high-dielectric solvents but less so for weakly polar and nonpolar solvents. The formal connection between C-PCM and the GB model suggests that C-PCM calculations place a limit on the accuracy that one should expect from GB models but also demonstrates that comparison of GB and C-PCM calculations directly interrogates the accuracy of the effective Coulomb operator that is used in the pairwise GB energy expression. We introduce a simple alternative to the "canonical" pairwise interaction operator first proposed by Still et al. and show that this alternative reduces the cost of the pairwise GB energy summation by as much as a factor of 3. At the same time, the new operator reduces statistical errors in solvation energies (as compared to C-PCM benchmarks) by 0.3% with respect to the canonical operator that exhibits an error of roughly 1.0%.