We consider four potential dyads: three from the SNase variant (PDB: 3BDC ) and one from protein deglycase DJ-1 The three SNase pairs exhibited different levels of coupling: the D21-D83 dyad showed almost no coupling (Figure ), as evidenced by the absence of inflection points in the ∆G and pK a curves, the D21-D40 showed moderate coupling (Figure ), and the D21-D19 dyad showed significant coupling (Figure ). In this latter case, as in the second toy example, the residues clearly acted to buffer one another, resulting in a flattening of ∆G for both curves around pH ∈ [3, 5].