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

Aarhus University, Aarhus, Denmark,

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.