ENERGY AND ENERGY DERIVATIVES FOR MOLECULAR SOLUTES - PERSPECTIVES OFAPPLICATION TO HYBRID QUANTUM AND MOLECULAR METHODS

We examine the state of the art of the solvation procedure called the polarizable continuum model (PCM), focusing our attention on the basic properties: energy of the solute, solvation energy, and their derivat ives with respect to nuclear coordinates. The PCM method is based on t he use of an effective solute Hamiltonian, where the solute-solvent po tential is described in terms of continuous response functions with bo undary conditions given in terms of the solute cavity surface. This ex position is mainly based on recent progress, a large part of which is still in press. The new procedures are quite effective, at the ab init io quantum mechanical level, but cannot be applied to very large solut es for the limitations of computer hardware. We introduce then other m ethods, presented here for the first time, which make possible the cla ssical calculation of the solvation energy also for very large solutes (a few thousand atoms). The strategy outlined here regards a new meth od to define cavity surfaces (supplemented with analytical definitions of its partition in tesserae) and of their derivatives, combined with a fast noniterative method to compute solvation energy. Finally, we d iscuss the introduction of this procedure in hybrid quantum mechanical /molecular mechanics descriptions of large solutes (enzymes), where th e quantum description is limited to the reacting portion of the enzyme . (C) 1996 John Wiley & Sons, Inc.