  Zinc is found saturated in the deposited Amyloid-beta (AB) peptide plaques in
brains of patients subjected to Alzheimer disease (AD). Zinc binding to AB
promotes aggregations, including the toxic soluble AB species. Up to now, only
the region 1-16 of AB complexed with Zinc (AB16-Zn) is defined structurally in
experiment, requiring an efficient theoretical method to present the
interaction between zinc and AB peptide. In order to explore the induced
polarization effect on the global conformation fluctuations and the
experimentally observed coordination mode of AB16-Zn, in this work we consider
an all-atom molecular dynamics (MD) of AB16-Zn solvated in implicit water. In
our model the polarization effect affects the whole peptide is applied. The
induced dipoles are divided into three distinct scales according to their
distances from zinc. Besides, the atomistic polarizability on the coordinating
sidechains is rescaled to describe the electron redistribution effect. As a
comparison, another model which exactly follows the method of Sakharov and Lim
(J. Am. Chem. Soc., 127, 13, 2005) has been discussed also. We show that,
associated with proper van der Waals (vdW) parameters, our model not only
obtains the reasonable coordinating configuration of zinc binding site, but
also retains the global stabilization, especially the N-terminal region, of the
AB16-Zn. We suggest that it is the induced polarization effect that promotes
reasonable solvent exposures of hydrophobic/hydrophilic residues regarding
zinc-induced AB aggregation.
