Semiclassical-Continuum Approach to the Electrostatic Free Energy of Solvation

Abstract

A new semiclassical continuum approach for computation of the electrostatic contribution to the free energy of solvation is presented. The method is based on a first-order perturbation treatment of the linear response approximation for the solvent effect. The expression for the electrostatic free energy of solvation afforded by the perturbative approach is formally similar to the classical continuum algorithm reported by Miertus, Scrocco, and Tomasi. Nevertheless, the semiclassical approach allows an accurate, inexpensive treatment of polarization effects, which relies on the use of two sets of partial charges for description of the solute-solvent interactions. The two sets of charges reflect the charge distribution of the solute in the gas phase and fully relaxed in solution. Particular attention is paid to the parametrization of the partial charges. The results determined by using the semiclassical approach for a series of prototypical neutral polar molecules, for selected amino acid residues in neutral and zwitterionic states, and for several test calculations on peptides are very close to the values determined from quantum mechanical self-consistent reaction field calculations. These encouraging results allow us to examine the potential application of the semiclassical treatment as a fast procedure for the inclusion of solvent polarization effects in force-field-derived methods.