An an exemplary application, we tested HetPCM with ε nonp = 4 and 10 for prediction of pK a values in a set of Cu proteins, using ε nonp to represent hydrophobic parts of a protein model and ε solv = 78.4 for solvent-exposed parts, for the purpose of DFT calculations. Reasonable agreement with experiment is obtained, which is vastly superior to the use of vacuum boundary conditions. HetPCM may thus represent a simple means to implement heterogeneous dielectric boundary conditions for cluster-QM enzymatic modeling with electronic structure theory.