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

Abstract The aggregation of human islet amyloid polypeptide (hIAPP) can damage the membrane of the β-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 t...

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Autores principales:	Na Liu, Mojie Duan, Minghui Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0183a43688614fc2b079b7a9966999ad
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spelling	oai:doaj.org-article:0183a43688614fc2b079b7a9966999ad2021-12-02T12:30:44ZStructural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations10.1038/s41598-017-08504-x2045-2322https://doaj.org/article/0183a43688614fc2b079b7a9966999ad2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08504-xhttps://doaj.org/toc/2045-2322Abstract The aggregation of human islet amyloid polypeptide (hIAPP) can damage the membrane of the β-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 α-helical states, β-sheet states, and fully disordered states, are identified. The formation of N-terminal β-sheet structure is prior to the C-terminal β-sheet structure towards the final fibril-like structures. The α-helical intermediates have lower propensity in the dimeric hIAPP and are off-pathway intermediates. The simulations also demonstrate that the β-sheet intermediates induce more perturbation on the membrane than the α-helical and disordered states and thus pose higher disruption ability.Na LiuMojie DuanMinghui YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Na Liu Mojie Duan Minghui Yang Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations
description	Abstract The aggregation of human islet amyloid polypeptide (hIAPP) can damage the membrane of the β-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 α-helical states, β-sheet states, and fully disordered states, are identified. The formation of N-terminal β-sheet structure is prior to the C-terminal β-sheet structure towards the final fibril-like structures. The α-helical intermediates have lower propensity in the dimeric hIAPP and are off-pathway intermediates. The simulations also demonstrate that the β-sheet intermediates induce more perturbation on the membrane than the α-helical and disordered states and thus pose higher disruption ability.
format	article
author	Na Liu Mojie Duan Minghui Yang
author_facet	Na Liu Mojie Duan Minghui Yang
author_sort	Na Liu
title	Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations
title_short	Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations
title_full	Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations
title_fullStr	Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations
title_full_unstemmed	Structural Properties of Human IAPP Dimer in Membrane Environment Studied by All-Atom Molecular Dynamics Simulations
title_sort	structural properties of human iapp dimer in membrane environment studied by all-atom molecular dynamics simulations
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0183a43688614fc2b079b7a9966999ad
work_keys_str_mv	AT naliu structuralpropertiesofhumaniappdimerinmembraneenvironmentstudiedbyallatommoleculardynamicssimulations AT mojieduan structuralpropertiesofhumaniappdimerinmembraneenvironmentstudiedbyallatommoleculardynamicssimulations AT minghuiyang structuralpropertiesofhumaniappdimerinmembraneenvironmentstudiedbyallatommoleculardynamicssimulations
_version_	1718394316412420096

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

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