Previous work has illustrated that an accurate determination of the pK a may require accounting for residue coupling. With respect to cysteine residues, often found at enzyme active sites, the relevance of coupling is expected to become even more pronounced. Elsewhere, we introduced a coupling formalism that improved pK a prediction accuracy; here, we apply this approach to twelve cysteine residues found near other titratable groups. Consistent with previous work, the pK a values of coupled residues were predicted with lower accuracy, when the coupling was not explicitly accounted for. Accounting for coupling, however, could in part remedy this (Figure ).