ANALYSIS OF PROTEIN METAL-BINDING SELECTIVITY IN A CLUSTER MODEL

Ab initio molecular orbital calculations of the binding energy of metal cations to octahedral clusters of water, formamide, and formate ligands are used to analyze Ca binding sites in proteins. The intrinsic energetics of the first coordination shell provide a basis for evaluating the conformation behavior and the selectivity of cation binding. The enthalpies of binding are modeled by estimating the environmental polarization energy relative to the model cluster of the first shell. Cluster reaction energies are calculated for transferring Mg, Ca, and Na cations from a water cluster to the protein model cluster as a function of metal-ligand distance which is found to strongly affect cation binding selectivity between cations of the same and different charges. The selectivity is a function of both steric and electrostatic interactions. As is well-known selectivity between cations of the same charge is dependent on steric factors, but there is also an electrostatic component, independent of steric influences, which is selective between cations of different charge. The data are applied to an analysis of two Ca binding sites in the protein, Subtilisin BPN'. The cluster model shows that ion desolvation energies determine the ion selectivity between Mg and Ca in the buried site. Interligand repulsion in the octahedral cluster prevents the larger formamide ligand from approaching the smaller Mg cation as closely as it does for single ligand binding. For the surface binding site, competition between cations of different charge, Ca and Na, can be understood in terms of the rigidity of the site cavity. © 1993, IEEE. All rights reserved. © 1990, American Chemical Society. All rights reserved.