Molecular mechanics (MM), molecular dynamics (MD) and semi-empirical study of Co2+, Cu2+, Ni2+ and Cd2+ binding to N-terminal of human serum albumin (HSA)

Molecular mechanics (MM) calculations coupled with molecular dynamics (MD) simulations have been used to model the geometries of the transition metal ions Co2+, Cu2+, Ni2+ and Cd2+ with the N-terminal of human serum albumin (HSA) using HyperChem 6.0 computational package. A simple procedure in which peptide constructs of 2-12 amino acids of the N-terminal HSA sequence are assigned partial charges on the basis of ZINDO/1 calculations and the metal ions are allowed to bind electrostatically to the peptides, produces results which are compatible with crystallographic data and previous H-1-NMR results. Modifications introduced to the N-terminal of the dodecapeptide construct, by way of mutations and the removal of specific amino acids, exhibit a reduction in the binding of CO2+. Also, peptides constructed using N-terminals of albumin from species other than human showed a similar reduction in their Co2+ binding capacity. These findings explain the indispensability of Asp-Ala-His residues in CO2+ binding confirming the reduction in in vitro binding of exogenous Co2+ to the N-terminal of HSA in patients suffering from myocardial ischemia. (C) 2004 Elsevier B.V. All rights reserved.