Modeling short-range contributions to hydration energies with minimal parameterization

A novel model of short-range contributions to hydration free energies is introduced for use with dielectric continuum treatment of long-range bulk electrostatics. The empirical model invokes extrema of the solute normal electric field at the cavity surface that nominally separates solute from solvent. It involves only a small handful of adjustable parameters, which are fitted to experimental data on a large collection of neutral and ionic solutes. The results show mean unsigned errors from experiment of only 0.9 kcal/mol for neutrals and 2.4 kcal/mol for ions, which are comparable to the best analogous previous efforts that utilize many more parameters.