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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