Zn2+ Effect on Structure and Residual Hydrophobicity of Amyloid β‑Peptide Monomers
2014-09-04T00:00:00Z (GMT) by
The aggregation of amyloid β-peptide (Aβ peptide) has been associated with the pathogenesis of Alzheimer’s disease (AD). In the present study, we aimed to disclose how Zn2+ affects the Aβ aggregation in detail. Thus, molecular dynamics simulation was implemented to elucidate the changes of structure and residual hydrophobicity upon Zn2+ coordination. Our results show that Zn2+ can strongly influence the structural properties of Aβ40 and Aβ42 by reducing helical formation and increasing turn formation to expose the hydrophobic regions. Furthermore, hydrophobicity of Zn2+-Aβ40 and Zn2+-Aβ42 was much higher than that of each monomer, since Zn2+ binding can significantly influence the hydrophilic domains of Aβ. The further analyses indicate that not only four residues (H6, E11, H13, and H14) but also R5, D7, K16, K28, and terminal residues influence hydrophobicity upon Zn2+ coordination. Importantly, R5, K16, and K28 play a crucial role to regulate solvation-free energies. This work is helpful to understand the fundamental role of Zn2+ in aggregation, which could be useful for further development of new drugs to inhibit Zn2+-Aβ aggregation.