All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints

doi:10.1002/prot.25677

	All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints
	Su, Xinyue 1,2; Wang, Ke 2,3; Liu, Na 2,3; Chen, Jiawen 2; Li, Yong 1; Duan, Mojie 2
刊名	PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
	2019-07-01
卷号	87 期号:7 页码:541-550
关键词	aggregation chemical shift restraint islet amylod polypeptide metadynamics
ISSN号	0887-3585
DOI	10.1002/prot.25677
英文摘要	Exploring the accurate structure ensembles are critical to understand the functions of intrinsically disordered proteins (IDPs). As a well-known IDP, islet amyloid polypeptide (IAPP) plays important roles in the development of human type II diabetes (T2D). The toxicity of human IAPP (hIAPP) is induced by the amyloidosis of the peptide, however, its aggregation mechanism remains ambiguous. The characterization of structure ensemble of hIAPP, as well as the differences between hIAPP and its non-amyloidogenic homologous such as rat IAPP (rIAPP), would greatly help to illuminate the amyloidosis mechanism of IAPP. In this study, the atomic structure ensembles of hIAPP and rIAPP were characterized by all-atom molecular dynamics (MD) simulations combined with enhanced sampling technology and experiment data restraints. The obtained structure ensembles were firstly compared with those determined by the conventional MD (cMD) and enhanced sampling without experiment data restraints. The results showed that the enhanced sampling and experiment data restraints would improve the simulation accuracy. The transient N-terminal alpha-helix structures were adopted by the sub-states of both hIAPP and rIAPP, however, the C-terminal helical structures were only present on hIAPP. The hydrophobic residues in the amyloid-core region of hIAPP are exposed to the solvent. The structure ensemble differences between hIAPP and rIAPP revealed in this work provide potential explain to the amyloidogenic mechanism and would be helpful for the design of drugs to combat T2D.
资助项目	National Natural Science Foundation of China[21773298] ; National Natural Science Foundation of China[21403291]
WOS关键词	MOLECULAR-DYNAMICS SIMULATIONS ; ALPHA-HELICAL STATES ; HUMAN AMYLIN ; SECONDARY STRUCTURE ; SIDE-CHAIN ; IAPP ; PROTEINS ; SPECTROSCOPY ; MECHANISM ; PEPTIDES
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	WILEY
WOS记录号	WOS:000469937400002
资助机构	National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/14448]
专题	中国科学院武汉物理与数学研究所
通讯作者	Li, Yong; Duan, Mojie
作者单位	1.Cent China Normal Univ, Dept Phys, 152 Luoyu Rd, Wuhan 430079, Hubei, Peoples R China 2.Chinese Acad Sci, CAS Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan,Wuhan Inst Phys &, Wuhan, Hubei, Peoples R China 3.Univ Chinese Acad Sci, Dept Chem, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Su, Xinyue,Wang, Ke,Liu, Na,et al. All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints[J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,2019,87(7):541-550.
APA	Su, Xinyue,Wang, Ke,Liu, Na,Chen, Jiawen,Li, Yong,&Duan, Mojie.(2019).All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints.PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,87(7),541-550.
MLA	Su, Xinyue,et al."All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints".PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 87.7(2019):541-550.