Selectivity of the chelator-protein interactions: A high level quantum chemistry study

We have employed correlated ab-initio and density functional theory (DFT) calculations to elucidate the selectivity of the interactions between chelators, which include -N-(CH₂-COO-)_n fragments and which coordinate di- and trivalent transition metal atoms and amino acids, with electron donor residues (histidine, cystein, methionine). The aim of the study is to initiate compilation of a database for such interactions based on the results obtained from the calculations. We found that an optimal (reliable and yet not too computationally damaging) approach for obtaining accurate interaction energies between chelators and amino acid residues involves an equilibrium geometry calculation at the DFT/6-31G* (for C, N, O, S, H atoms)/VTZ (for metal atoms) level of theory followed by a MP2 energy calculation performed at the DFT equilibrium geometry with the aug-cc-pVDZ VTZ basis set. The most accurate interaction energies were obtained when the water molecules belonging to the first coordination sphere were included in the calculations. Also, accounting for the zero-point vibrational energy correction and the basis set superposition energy correction aided the accuracy of the calculations. The interaction energy calculations performed for the chosen set of chelators, metal ions (Zn²⁺, Co²⁺, Fe²⁺, Ni²⁺ Cu²⁺ Pd²⁺, Cd²⁺), and amino acid residues allowed us to elucidate the selectivity of the interactions.