Potentials of Mean Force and Solvent Structure

With respect to the technical challenges involved, continuum models that use a cavity-based approach to solve the Poisson equation are not well suited to computing PMFs. The problem is that it is quite difficult to solve the necessary equations when there are two cavities. Moreover, when the two cavities first touch one another and begin to penetrate, the narrow neck of the joined cavities can lead to numerical instabilities. 

Generalized Bom models do not suffer from the multiple cavity problem, which is a particular advantage of that methodology. However, initial studies have suggested that 

It is sometimes the case that the stmetme of the first shell (or shells) of solvent is a property of primary interest for a given modeling study. It is perhaps stating the obvious to note that in such an instance, continuum models cannot be used, since by construction they ignore the molecular natme of the solvent and assume a homogeneous surrounding medium. 

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