and in several of the charge-neutral cases the percentage errors in ∆G elst are rather large. For example, phenol exhibits the largest differences absolute differences in ∆G elst amongst the neutral solutes (at 2 kcal/mol), which translates into relative errors as large as 118% since the Voronoi-PEqS benchmarks lie in the range |∆G elst | = 4-6 kcal/mol. However, these deviations are substantially reduced simply by increasing ε nonp from 1 to 2 (Table ). For the combination of ε nonp = 2 and ε solv = 78.4, the maximum deviation between the HetPCM and Voronoi-PEqS methods is no greater than 1.7 kcal/mol (41% of ∆G elst ) for the neutral solutes. (Including the ions, the average deviation is 4.8 kcal/mol.) Although the change from ε nonp = 1 to 2 seems quite modest, there is precedent for such a change inducing relatively large changes in reaction energies in QM/PCM calculations on cluster models of enzymes. Those changes are often large upon passing from vacuum dielectric boundaries to ε = 2, with the effect saturating by ε = 4. The agreement between HetPCM and Voronoi-PEqS improves even further for ε nonp = 4 or 10, as demonstrated in Table . For ε nonp = 4, which is often used to represent the hydrophobic interiors of proteins, the absolute differences for charge-neutral solutes are all < 2 kcal/mol, which is no more than a 32% error, while the errors for ions are all < 10%. For ε nonp = 10, this difference drops to 2% for both neutral and ionic solutes.