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 Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+ cations were computed with DFT/B3LYP method. Four coordination geometries, which ar e most frequently encountered in the metal-binding sites of metalloproteins and smaller-molecule crystal structures (octahedral, square planar, tetrah edral, and linear), were considered for each metal ion. The computational s trategy consisted of several steps. First, the affinities of studied metal ions for (H2O)(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 be en calculated. Together, it gives an insight into the molecular structure o f metal-binding sites of metalloproteins and provides an accurate quantific ation of the affinity and selectivity of amino acid side chains for the stu died 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.