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As a well\u2010known 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\u2010amyloidogenic 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\u2010atom 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\u2010terminal \u03b1\u2010helix structures were adopted by the sub\u2010states of both hIAPP and rIAPP, however, the C\u2010terminal helical structures were only present on hIAPP. The hydrophobic residues in the amyloid\u2010core 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.<\/jats:p>","DOI":"10.1002\/prot.25677","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T06:26:08Z","timestamp":1551162368000},"page":"541-550","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["All\u2010atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints"],"prefix":"10.1002","volume":"87","author":[{"given":"Xinyue","family":"Su","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan Wuhan Institute of Physics and Mathematics, Chinese Academy of 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China"},{"name":"Department of Chemistry University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawen","family":"Chen","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physics Central China Normal University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-832X","authenticated-orcid":false,"given":"Mojie","family":"Duan","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of magnetic Resonance in Biological Systems, State Key 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