THE MEANING OF COMPONENT ANALYSIS - DECOMPOSITION OF THE FREE-ENERGY IN TERMS OF SPECIFIC INTERACTIONS

Free energy simulations are of particular interest for the interpretat ion of macroscopic data in terms of microscopic interactions. This can be done by expressing calculated free energies as a sum of components that correspond to the contributions of different energy terms or dif ferent parts of the system. Since the resulting components depend on t he integration path, care is required in their use. We show that a lin ear coupling scheme for the alchemical creation of a chemical identity corresponds to a particularly useful path because it leads to a symme tric decoupling of the free energy components. The path dependence als o provides an additional degree of freedom that can be used to study d ifferent processes. This latter point is illustrated by a reinterpreta tion of a recent simulation on wild-type and mutant azurin by Mark and van Gunsteren. (C) 1995 Academic Press Limited