Molecular Modeling of Amyloid Aggregation

David Bevan, Virginia Polytechnic Institute and State University

Usage Details

This project is part of the Blue Waters Student Internship Program. This project focuses on molecular dynamics simulation of amyloid beta oligomers both in solution and in a complex with a membrane. The self-assembly of amyloidogenic peptides into cytotoxic oligomers and amyloid fibrils is associated with several progressive diseases including Alzheimer's disease and type II diabetes. The details of this self-assembly and the effects of these oligomers, especially low molecular weight oligomers (dimers to dodecamers), on plasma membranes is largely unknown. By investigating the molecular details and interactions associated with oligomer assembly and the interactions of the oligomers with membranes, we can provide insight into mechanistic details relevant to toxicity. This project investigates the formation of low-molecular weight oligomers in a range of sizes to determine key size and environmental influences on the fibril formation and perturbation of model membranes by the oligomers. The intern will build systems of nontruncated amyloid beta ranging in size from two amyloid beta molecules up to twelve amyloid beta molecules and simulate the molecular dynamics of these systems over a timescale of 1 microsecond.