文献类型：期刊文献

英文题名：Zn2+ Binding Increases Parallel Structure in the Aβ(16-22) Oligomer by Disrupting Salt Bridge in Antiparallel Structure

作者：Song, Yongshun[1];Wu, Mengjiao[1];Wang, Changying[2];Fang, Haiping[1,3];Lei, Xiaoling[1]

机构：[1]East China Univ Sci & Technol, Sch Phys, Shanghai 200237, Peoples R China;[2]Changzhou Inst Technol, Sch Sci, Changzhou 213032, Peoples R China;[3]Zhejiang Normal Univ, Dept Phys, Jinhua 321004, Peoples R China

年份：2024

卷号：128

期号：6

起止页码：1385

外文期刊名：JOURNAL OF PHYSICAL CHEMISTRY B

收录：;EI(收录号：20240715549084);WOS:【SCI-EXPANDED(收录号:WOS:001158986100001)】；

基金：The authors thank Dr. Shanshan Liang, Dr. Shiqi Sheng, and Dr. Yingying Huang for their constructive suggestions. Support from the National Natural Science Foundation of China (grant nos. 11974366, 22302018), the Fundamental Research Funds for the Central Universities of China, the Guanghe Fund (the second phase), and the Shanghai Supercomputer Center of China is acknowledged.

语种：英文

外文关键词：Glycoproteins - Metal ions - Molecular dynamics - Peptides

摘要：The aggregation of monomeric amyloid beta protein (A beta) into oligomers and amyloid plaque in the brain is associated with Alzheimer's disease. The hydrophobic central core A beta(16-22) has been widely studied due to its essential role in the fibrillization of full-length A beta peptides. Compared to the homogeneous antiparallel structure of A beta(16-22) at the late stage, the early-stage prefibrillar aggregates contain varying proportions of different beta structures. In this work, we studied the appearance probabilities of various self-assembly structures of A beta(16-22) and the effects of Zn2+ on these probabilities by replica exchange molecular dynamics simulations. It was found that at room temperature, A beta(16-22) can readily form assembled beta-sheet structures in pure water, where a typical antiparallel arrangement dominates (24.8% of all sampled trimer structures). The addition of Zn2+ to the A beta(16-22) solution will dramatically decrease the appearance probability of antiparallel trimer structures to 12.5% by disrupting the formation of the Lys16-Glu22 salt bridge. Meanwhile, the probabilities of hybrid antiparallel/parallel structures increase. Our simulation results not only reveal the competition between antiparallel and parallel structures in the A beta(16-22) oligomers but also show that Zn2+ can affect the oligomer structures. The results also provide insights into the role of metal ions in the self-assembly of short peptides.