AB-INITIO FREE-ENERGY PERTURBATION CALCULATIONS OF SOLVATION FREE-ENERGY USING THE FROZEN DENSITY-FUNCTIONAL APPROACH

Ab initio free energy perturbation calculations of solvation free ener gies are performed using the recently developed frozen density functio nal method. This method treats the solute-solvent system as a supermol ecule in the density functional formulation but freezes the the electr on density of the solvent molecules, while considering its effect on t he solute Hamiltonian. The quality of the intermolecular interactions obtained by this method ; is examined by-calculating the potential sur face for a water dimer composed of one solute and one solvent molecule . The resulting potential surface provides a good approximation for th e actual intermolecular potential of the water dimer. The same approac h is then used in evaluating the solvation free energy of a water mole cule relative to the corresponding solvation free energy of a methane molecule. These ab initio solvation free energies are calculated by us ing a classical force field as a reference for the corresponding quant um mechanical energy surface. The results of the calculations are enco uraging indicating that the frozen density functional method can be ap plied to studies of chemical reactions in solutions. Furthermore, the use of a classical force field as a reference state should provide a g eneral way for performing free energy perturbation calculations by any ah initio method.