Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations

doi:10.1038/s41598-017-08504-x

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	Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations
	Liu, Na 1,2; Yang, Minghui 2; Duan, Mojie 2
刊名	SCIENTIFIC REPORTS
	2017-08-11
卷号	7
DOI	10.1038/s41598-017-08504-x
文献子类	Article
英文摘要	The aggregation of human islet amyloid polypeptide (hIAPP) can damage the membrane of the beta-cells in the pancreatic islets and induce type 2 diabetes (T2D). Growing evidences indicated that the major toxic species are small oligomers of IAPP. Due to the fast aggregation nature, it is hard to characterize the structures of IAPP oligomers by experiments, especially in the complex membrane environment. On the other side, molecular dynamics simulation can provide atomic details of the structure and dynamics of the aggregation of IAPP. In this study, all-atom bias-exchange metadynamics (BE-Meta) and unbiased molecular dynamics simulations were employed to study the structural properties of IAPP dimer in the membranes environments. A number of intermediates, including alpha-helical states, beta-sheet states, and fully disordered states, are identified. The formation of N-terminal beta-sheet structure is prior to the C-terminal beta-sheet structure towards the final fibril-like structures. The alpha-helical intermediates have lower propensity in the dimeric hIAPP and are off-pathway intermediates. The simulations also demonstrate that the beta-sheet intermediates induce more perturbation on the membrane than the alpha-helical and disordered states and thus pose higher disruption ability.
WOS关键词	ISLET AMYLOID POLYPEPTIDE ; TYPE-2 DIABETES-MELLITUS ; ALPHA-HELICAL STATES ; LIPID-MEMBRANES ; HUMAN AMYLIN ; A-BETA ; PROTEIN ; MECHANISM ; AGGREGATION ; FIBRILS
WOS研究方向	Science & Technology - Other Topics
语种	英语
WOS记录号	WOS:000407442500055
资助机构	National Natural Science Foundation of China(21403291) ; National Natural Science Foundation of China(21403291) ; National Natural Science Foundation of China(21403291) ; National Natural Science Foundation of China(21403291)
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/11360]
专题	武汉物理与数学研究所_理论与交叉研究部
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Key Lab Magnet Resonance Biol Syst,Natl Ctr Magne, Wuhan 430071, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Liu, Na,Yang, Minghui,Duan, Mojie. Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations[J]. SCIENTIFIC REPORTS,2017,7.
APA	Liu, Na,Yang, Minghui,&Duan, Mojie.(2017).Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations.SCIENTIFIC REPORTS,7.
MLA	Liu, Na,et al."Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations".SCIENTIFIC REPORTS 7(2017).