Theoretical Studies of Metal Ion Selectivity. 1. DFT Calculations of Interaction Energies of Amino Acid Side Chains with Selected Transition Metal Ions (Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, and Hg²⁺)

The interaction energies of functional groups representing the side chains of amino acid residues with Co 2+, Ni 2+, Cu 2+, Zn 2+, Cd 2+, and Hg 2+ cations were computed with DFT/B3LYP method. Four coordination geometries, which are most frequently encountered in the metal-binding sites of metalloproteins and smaller-molecule crystal structures (octahedral, square planar, tetrahedral, and linear), were considered for each metal ion. The computational strategy consisted of several steps. First, the affinities of studied metal ions for (H 2 O) n site, pre-organized in particular coordination geometry, have been evaluated. Second, the interaction energy of a single functional group with the transition metal ion of interest has been calculated, while the remaining coordination bonds were saturated with water molecules. Third, and finally, the effect of elongation of the amino acid side chain has been calculated. Together, it gives an insight into the molecular structure of metal-binding sites of metalloproteins and provides an accurate quantification of the affinity and selectivity of amino acid side chains for the studied metal ions. These two quantities play a key role in the metal-binding properties of proteins and peptides. The important implications in an area of bioinorganic chemistry are discussed as well.