COMPUTATION OF HYDRATION FREE-ENERGIES USING A PARAMETERIZED CONTINUUM MODEL - STUDY OF EQUILIBRIUM GEOMETRIES AND REACTIVE PROCESSES IN WATER SOLUTION

A parameterized self-consistent reaction field model allowing computat ion of the total free energy of hydration of organic molecules at the ab initio level is presented. The approach uses electrostatic plus pol arization energies calculated with the help of a continuum model. The remaining solvation free energy terms are obtained by a simple formula based on atomic parameters and atomic accessible surface areas (ASAs) , which are determined with the ASA analytical algorithm. Analytical d erivatives of the atomic surfaces areas have been implemented. The ato mic parameters have been obtained by a linear regression fit of the ca lculated and experimental free energies of solution in water for a set of 35 molecules, leading to a standard deviation of 0.75 kcal/mol. Ef fects of nonelectrostatic terms on solute geometries, association ener gies, and activation barriers are illustrated. (C) 1996 by John Wiley & Sons, Inc.