Calculation of ∆G elst is not actually our motivation to develop anisotropic continuum solvation models. A more compelling rationale for development of HetPCM is simply to have heterogeneous dielectric boundary conditions that can be applied to sizable biomolecular models, where it does not make sense to use the same dielectric constant for all residues because some of them may be solventexposed while others are buried within the hydropho- bic interior of the protein. What we desire is a qualitative means to provide compensating charge when an ionic residue is solvent-exposed, while not over-polarizing the hydrophobic regions with a large dielectric constant. In this way, HetPCM boundary conditions (combined with an atomistic quantum chemistry description of the solute) may provide a reasonable, qualitative description of the electrostatic potential in a QM model of a biomolecule. We explore that possibility directly in the present section.