Figure shows how the total charge on hisactophilin changes as a function of pH when ε ∞ = 4 and n 0 = 100 mM, both in presence and in absence of CR. In this particular case, the inclusion of CR effects does not significantly alter the predicted isoelectric point of the protein, pI ≈ 7.45 (CR) compared to pI ≈ 7.35 (no CR). The largest predicted difference at the same system parameters occurs for β-lactoglobulin, where the isoelectric point increases by more than half a unit in presence of CR, pI ≈ 5.55 (CR) compared to pI ≈ 4.95 (no CR)-see Fig. in the SI. This slightly overestimates the mea-sured values . We note that even in the absence of CR, certain structural and continuum electrostatic effects are included in the calculation as the dissociation constants of the AAs are determined by PROPKA (see also the SI).