The accurate calculation of the energetics of electrostatically driven binding of amino acid residues to other amino acids (salt bridges) or to synthetic molecules is critical in numerous physiological and technological processes. Commonly used continuum methods are unable to capture differences in interaction energies resulting from specific chemical changes, such as the stronger retention of basic proteins on sulfated (strong) than on carboxylated (weak) cation exchangers. The inadequacies of continuum models in describing hydration effects, specifically local solvent structure and associated polarization effects, are especially apparent in such systems. These shortcomings have been addressed by modeling the protein-cation exchanger interaction as that of methylammonium, a model for a protonated lysine residue, with the methylated analogues of the ion-exchange functionalities, namely methyl sulfate and acetate ion, respectively. A hybrid quantum-continuum treatment of the solvent is able to capture the qualitative differences in binding that are not obtained by continuum methods. More remarkably, it is seen that a heuristic approach, based solely on the bulk solvation foe energies of individual species, is able to describe qualitatively the differences in binding.