SEMICLASSICAL-CONTINUUM APPROACH TO THE ELECTROSTATIC FREE-ENERGY OF SOLVATION

A new semiclassical continuum approach for computation of the electros tatic contribution to the free energy of solvation is presented. The m ethod is based on a first-order perturbation treatment of the linear r esponse approximation for the solvent effect. The expression for the e lectrostatic free energy of solvation afforded by the perturbative app roach is formally similar to the classical continuum algorithm reporte d by Miertus, Scrocco, and Tomasi. Nevertheless, the semiclassical app roach allows an accurate, inexpensive treatment of polarization effect s,which relies on the use of two sets of partial charges for descripti on of the solute-solvent interactions. The two sets of charges reflect the charge distribution of the solute in the gas phase and fully rela xed in solution. Particular attention is paid to the parametrization o f the partial charges. The results determined by using the semiclassic al approach for a series of prototypical neutral polar molecules, for selected amino acid residues in neutral and zwitterionic states, and f or several test calculations on peptides are very close to the values determined from quantum mechanical self-consistent reaction field calc ulations. 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 meth ods.