Polarization effect of zinc on the region 1-16 of amyloid-beta peptide: a molecular dynamics study

Zinc is found saturated in the deposited Amyloid-beta ( β A ) peptide plaques in Alzheimer’s disease (AD) patients’ brains. Zinc binding to β A promotes aggregations, including the toxic soluble β A species. Up to now, only the region 1-16 of β A complexed with Zinc ( 16 1− β A -Zn ) is defined structurally in experiment, requiring an efficient theoretical method to present the interaction between zinc and β A peptide. In order to explore the induced polarization effect on the global conformation fluctuations and the experimentally observed coordination mode of 16 1− β A -Zn, in this work we consider an all-atom molecular dynamics (MD) of 16 1− β A -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 Sakharov and Lim’s method (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 16 1− β A -Zn. We suggest that it’s the induced polarization effect that promotes reasonable solvent exposures of hydrophobic/hydrophilic residues regarding zinc-induced β A aggregation.