Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

13-POS Board 13 Modelling the Self-Assembly of Islet Amyloid Polypeptide Mikkel Christensen 1,2,2 , Katrine K. Skeby 1,2 , Birgit Schiøtt 1,2 .

1 Aarhus University, Aarhus, Denmark, 2 Interdisciplinary Nanoscience Center, Aarhus, Denmark. Islet amyloid polypeptide (IAPP) is an amyloid peptide that forms structures with a cytotoxic activity; thereby decreasing the number of insulin producing cells in patients with type II diabetes mellitus. While the nature of the cytotoxic structures is unknown; mature amyloid fibrils of IAPP have been isolated from living tissue and non-selective and membrane-perforating pores of IAPP has been observed in experiments. Many researchers seek to learn about these structures to find a way to slow down the development of the disease. With all-atom molecular dynamics simulations combined with the Highly Mobile Membrane Mimetic Model (HMMM) with enhanced sampling of membrane dynamics, we have investigated the membrane interaction and self-assembly of this IAPP peptides. The focus is on the initial self-assembly and how lipid membranes induce the transformation from monomers to oligomers. We have observed the transition from alpha-helical monomers to stable beta-sheet containing assemblies. With this we have identified regions of the peptide that are important for the inter-peptide recognition and for connecting the peptides in beta-sheets. These results support current experimental findings and can be used to explain experimental results in atomistic models, and inspire future experimental and computational studies of the peptide.

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