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The aggregation of human islet amyloid polypeptide(IAPP)has an important implication in type 2 diabetes.The cytotoxicity of IAPP is proposed to be associated with the membrane damage of the β-cells in the pancreatic islets.Due to the fast aggregation rate of IAPP on the membrane,the detailed mechanism of IAPP amyloid fibril formation remains unclear.In this study,the bias exchange metadynamics simulations were employed to study the dimerization process of IAPP on the membranes.Our simulations revealed that the on-pathway intermediate states mainly involved the beta-strand structures.Besides,unlike in the aqueous environment,there is no need to form ordered structure for the loop region of IAPP in the dimerization process.Our simulation results would help to uncover the mechanism of IAPP aggregation and to design novel drugs to inhibit the formation of hIAPP fibrls.