Insights into the Conformational Ensemble of Human Islet Amyloid Polypeptide from Molecular Simulations

Author(s): Linh Tran, Tap Ha-Duong

Journal Name: Current Pharmaceutical Design

Volume 22 , Issue 23 , 2016

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Background: The human islet amyloid polypeptide (hIAPP) can form insoluble fibrillar aggregates in the pancreas of patients with type 2 diabetes. However, increasing evidence suggests that, rather than the fibrils themselves, the hIAPP oligomers that appear on the fibrillation pathway are the toxic species for the pancreatic β -cells. In the perspective of designing therapeutic inhibitors of hIAPP aggregation, it is thus crucial to better understand the mechanism of formation and to characterize the structures of these intermediate species. Methods: However, it still remains a great challenge to experimentally study the hIAPP conformations, due to its intrinsically disordered characteristic and its fast aggregation propensity. Therefore, theoretical and computational approaches were used by many groups as complementary methods to investigate the hIAPP structural features involved in its oligomerization process. Conclusion: In this review, we examine the results provided by the hIAPP molecular simulations, in order to identify convergent insights into its conformational ensemble. Since hIAPP aggregation was shown to be modulated by the presence of lipid membranes, we survey molecular modeling studies of the peptide both in solution and membrane environment.

Keywords: Type 2 Diabetes, IAPP monomer, IAPP oligomer, Molecular Dynamics, Intrinsically Disordered Protein, Self-aggregation, Protein-Membrane Interaction, Conformational transition.

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Article Details

Year: 2016
Published on: 13 June, 2016
Page: [3601 - 3607]
Pages: 7
DOI: 10.2174/1381612822666160414142538
Price: $65

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