Effects of zinc binding on the conformational distribution of the amyloid-β peptide based on molecular dynamics simulations
Effects of zinc binding on the conformational distribution of the amyloid-β peptide based on molecular dynamics simulations
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DOI：
10.1021/jp076213t
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发表时间：
2007-12-13
影响因子：
3.3
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Li, Wenfei;Zhang, Jian;Wang, Wei
大量实验表明金属结合可以促进淀粉样β肽的聚集。在这项工作中。基于广泛的分子动力学模拟，研究了锌结合对全长淀粉样蛋白-P 肽构象分布的影响。通过比较脱辅基肽和全肽的构象分布，我们发现锌结合可以显着影响淀粉样蛋白-β单体的构象分布。与脱辅基肽相比，全息肽在中央疏水簇 17-21 上采样了更多的 β 链构象。同时，室温下盐桥Asp23-Lys28和包含23-28的转角的形成概率也显着增加。由于这些局部结构对于淀粉样蛋白-β 聚集至关重要，因此观察到的锌结合效应表明金属诱导的单体构象变化是金属促进淀粉样蛋白-β 肽聚集的可能机制之一。
A number of experiments suggested that metal binding can promote the aggregation of the amyloid-beta peptide. In this work. the effects of the zinc binding on the conformational distributions of the full length amyloid-P peptide are investigated on the basis of extensive molecular dynamics simulations. By comparing the conformational distributions of the apo-peptide and the holo-peptide, we show that the zinc binding can affect the conformational distribution of the amyloid-beta monomer dramatically. Compared with the apo-peptide, the holo-peptide samples more beta-strand conformation for the central hydrophobic cluster 17-21. Meanwhile, the formation probabilities of the salt bridge Asp23-Lys28 and the turn comprising 23-28 are also increased significantly at room temperature. Since these local structures are essential for the amyloid-beta aggregation, the observed effects of the zinc binding indicate that the metal induced conformational change of the monomer is one of the possible mechanisms for the metal promoted aggregation of the amyloid-beta peptide.