Carboxylate binding to be(2+) in proteins and influence of the dielectric environment

To gain insight into the interaction of Be2+ ions with negatively charged protein residues, the free energy changes associated with the replacement of water molecules in the first hydration shell of with one and two acetate anions were computed for the gas phase reactions using ab initio methods at the MP2 and DFT-B3LYP computational levels. Both unidentate and bidentate modes of coordination of the carboxylate group with the Be2+ ion are considered. Continuum dielectric calculations were then performed to estimate the corresponding free energy changes in several environments of varying dielectric strength. Environments with dielectric constants of 2 and 4, which represent a protein interior, and 78, which corresponds to water, were used. It is found that the free energy changes for the substitution reactions decrease in magnitude with increasing dielectric strength, in agreement with similar results reported for Mg2+, Ca2+, and Zn2+ (Dudev et al. J. Phys. Chem. B 2000, 104, 3692). However, unlike Mg2+, Ca2+, and Zn2+, the free energy change for single-anion or concerted two-anion substitution reactions with remains negative and indicates the reactions are still favorable in the high dielectric aqueous environment. It is also found that the unidentate mode of binding is favored over the bidentate mode, and this is attributed, in part, to the introduction of hydrogen bonds between one carboxylate oxygen and a water molecule within the cluster when unidentate binding with Be2+ is involved.