Computational insights into the inhibition and destabilization of morin on the oligomer of full-length human islet amyloid polypeptide

doi:10.1039/c5cp03991f

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	Computational insights into the inhibition and destabilization of morin on the oligomer of full-length human islet amyloid polypeptide
	Wang, QQ; Zhou, SY; Wei, W; Yao, XJ; Liu, HX; Hu, ZD; Liu, HX (reprint author), Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China.
刊名	PHYSICAL CHEMISTRY CHEMICAL PHYSICS
	2015
卷号	17 期号:43 页码:29103-29112
ISSN号	1463-9076
DOI	10.1039/c5cp03991f
文献子类	Article
英文摘要	The aggregation of human islet amyloid polypeptide (hIAPP) is closely related with the occurrence of type 2 diabetes (T2D). Natural flavonoid morin was confirmed to not only inhibit the amyloid formation of hIAPP, but disaggregate its preformed amyloid fibrils. In this study, with the goal of elucidating the molecular mechanism of inhibition and destabilization of morin on the full-length hIAPP1-37 oligomer, molecular dynamics simulations were performed for hIAPP1-37 pentamer in the presence and absence of morin. The obtained results show that during the protein-inhibitor interaction, morin can notably alter the structural properties of hIAPP1-37 pentamer, such as morphology, solvent accessible surface area and secondary structure. Moreover, we identified three possible binding sites of morin on hIAPP, all of which located near the amyloidogenic region of this protein. From the binding free energy calculations, we found that Site II was the most possible one. Further conformational analysis together with energy decomposition showed that the residues His18, Phe23 and Ile26 play a key role in the binding with morin by hydrogen bond, p-p and hydrophobic interactions. The proposal of the theoretical mechanism of morin against hIAPP aggregation will provide valuable information for the development of new drugs to inhibit hIAPP aggregation.
学科主题	Chemistry ; Physics
出版地	CAMBRIDGE
资助项目	国家自然科学基金项目 ; 中央高校基本科研业务费专项资金
项目编号	National Natural Science Foundation of China [21375054] ; Fundamental Research Funds for the Central Universities [lzujbky-2014-k21]
语种	英语
WOS记录号	WOS:000364024100073
资助机构	NSFC ; LZU
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/179521]
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,Zhou, SY,Wei, W,et al. Computational insights into the inhibition and destabilization of morin on the oligomer of full-length human islet amyloid polypeptide[J]. PHYSICAL CHEMISTRY CHEMICAL PHYSICS,2015,17(43):29103-29112.
APA	Wang, QQ.,Zhou, SY.,Wei, W.,Yao, XJ.,Liu, HX.,...&Liu, HX .(2015).Computational insights into the inhibition and destabilization of morin on the oligomer of full-length human islet amyloid polypeptide.PHYSICAL CHEMISTRY CHEMICAL PHYSICS,17(43),29103-29112.
MLA	Wang, QQ,et al."Computational insights into the inhibition and destabilization of morin on the oligomer of full-length human islet amyloid polypeptide".PHYSICAL CHEMISTRY CHEMICAL PHYSICS 17.43(2015):29103-29112.