Molecular modeling of the competitive substitution effect between Cu2+ and Zn2+ in the interactions with amyloid β-peptide

The possible mechanism of the competitive substitution effect between Zn2+ and Cu2+ in the interactions with A beta was investigated for the first time by a molecular modeling method. The results show that Zn2+ fails to substitute the Cu2+ in the complex of [Cu-H13(N pi)-Y10(OH)] with a quasi-helix conformation and thus is of no effect on the inhibition of Cu 2+ on AP aggregation. However, in striking contrast to Zn2+, Cu2+ effectively substitutes the Zn2+ in the complexes of [Zn-H14(N tau)-V12(CO)] and [Zn-H13(N tau)E11(CO)] almost without disturbing the conformation of the complexes. In addition, Cu2+ may even substitute the Zn2+ which crosslinks two AP strands by the bridge of [H13(N tau)-Zn-H14(N tau)].