Exploring the Influence of EGCG on the beta-Sheet-Rich Oligomers of Human Islet Amyloid Polypeptide (hIAPP(1-37)) and Identifying Its Possible Binding Sites from Molecular Dynamics Simulation

doi:10.1371/journal.pone.0094796

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	Exploring the Influence of EGCG on the beta-Sheet-Rich Oligomers of Human Islet Amyloid Polypeptide (hIAPP(1-37)) and Identifying Its Possible Binding Sites from Molecular Dynamics Simulation
	Wang, QQ; Guo, JJ; Jiao, PZ; Liu, HX; Yao, XJ; Liu, HX (reprint author), Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China.
刊名	PLOS ONE
	2014-04-16
卷号	9 期号:4 页码:-
ISSN号	1932-6203
DOI	10.1371/journal.pone.0094796
文献子类	Article
英文摘要	EGCG possesses the ability of disaggregating the existing amyloid fibrils which were associated with many age-related degenerative diseases. However, the molecular mechanism of EGCG to disaggregate these fibrils is poorly known. In this work, to study the influence of EGCG on the full-length human islet amyloid polypeptide 1-37 (hIAPP(1-37)) oligomers, molecular dynamics simulations of hIAPP(1-37) pentamer and decamer with EGCG were performed, respectively. The obtained results indicate that EGCG indeed destabilized the hIAPP(1-37) oligomers. The nematic order parameter and secondary structure calculations coupled with the free-energy landscape indicate that EGCG broke the initial ordered pattern of two polymers, greatly reduced their beta-sheet content and enlarged their conformational space. On this basis, three possible target sites were identified with the binding capacity order of S1>S2>S3. After a deeper analysis of each site, we found that S1 was the most possible site on which residues B-Ile26/Ala25, A-Phe23, B/C-Leu27 and E-Tyr37 played an important role for their binding. The proposal of this molecular mechanism can not only provide a prospective interaction figure between EGCG and beta-sheet-rich fibrils of hIAPP(1-37), but also is useful for further discovering other potential inhibitors.
学科主题	Science & Technology - Other Topics
出版地	SAN FRANCISCO
资助项目	国家自然科学基金项目
项目编号	National Natural Science Foundation of China [21103075, 21375054]
语种	英语
WOS记录号	WOS:000336863900067
资助机构	NSFC
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/122015]
专题	药学院_期刊论文
通讯作者	Liu, HX (reprint author), Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China.
推荐引用方式 GB/T 7714	Wang, QQ,Guo, JJ,Jiao, PZ,et al. Exploring the Influence of EGCG on the beta-Sheet-Rich Oligomers of Human Islet Amyloid Polypeptide (hIAPP(1-37)) and Identifying Its Possible Binding Sites from Molecular Dynamics Simulation[J]. PLOS ONE,2014,9(4):-.
APA	Wang, QQ,Guo, JJ,Jiao, PZ,Liu, HX,Yao, XJ,&Liu, HX .(2014).Exploring the Influence of EGCG on the beta-Sheet-Rich Oligomers of Human Islet Amyloid Polypeptide (hIAPP(1-37)) and Identifying Its Possible Binding Sites from Molecular Dynamics Simulation.PLOS ONE,9(4),-.
MLA	Wang, QQ,et al."Exploring the Influence of EGCG on the beta-Sheet-Rich Oligomers of Human Islet Amyloid Polypeptide (hIAPP(1-37)) and Identifying Its Possible Binding Sites from Molecular Dynamics Simulation".PLOS ONE 9.4(2014):-.