PATH DEPENDENCE OF FREE-ENERGY COMPONENTS IN THERMODYNAMIC INTEGRATION

In this article it is shown that the decomposition of free energy diff erences, as evaluated by molecular simulations using thermodynamic int egration, in terms of components corresponding to terms in the Hamilto nian, cannot be uniquely performed. This path dependence of the contri butions to the total free energy difference is shown for the calculate d difference in free energy of hydration of ethanol and ethane. The co nclusion of this study is that the individual free energy difference c ontributions from such calculations should, in general, be interpreted with care.