Zn2+ Effect on Structure and Residual Hydrophobicity of Amyloid 尾-Peptide Monomers

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• 作者：Hu Shi ; Baotao Kang ; Jin Yong Lee
• 刊名：Journal of Physical Chemistry B
• 出版年：2014
• 出版时间：September 4, 2014
• 年：2014
• 卷：118
• 期：35
• 页码：10355-10361
• 全文大小：458K
• ISSN：1520-5207

文摘

The aggregation of amyloid 尾-peptide (A尾 peptide) has been associated with the pathogenesis of Alzheimer鈥檚 disease (AD). In the present study, we aimed to disclose how Zn²⁺ affects the A尾 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 A尾40 and A尾42 by reducing helical formation and increasing turn formation to expose the hydrophobic regions. Furthermore, hydrophobicity of Zn²⁺-A尾40 and Zn²⁺-A尾42 was much higher than that of each monomer, since Zn²⁺ binding can significantly influence the hydrophilic domains of A尾. 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⁺-A尾 aggregation.