Abstract

Amyloid fibrils are insoluble protein aggregates with a characteristic molecular structure, that are associated with a variety of grave diseases in humans. Despite decades of research, much uncertainty remains regarding the pathological mechanisms of amyloid-associated diseases and the pathways by which soluble proteins self-assemble into cytotoxic oligomeric species and fibrils. The study of protein aggregation presents a significant challenge in both experiments and computer simulations, with the main difficulty associated with computational studies being the large system sizes and long timescales involved in protein self-assembly, which are far beyond those accessible with atomistic molecular modelling.

One solution to this is coarse-graining, which can allow dramatic increases in the system sizes under study and is a popular technique for the simulation of large-scale phenomena, however results obtained from coarse-grained simulations are inherently sensitive to the choice of model parameters and so a careful approach to parametrisation must be taken in order to obtain useful results. In this talk, I will be discussing my PhD project, which aims to develop a sequence-dependent coarse-grained model suitable for modelling the self-assembly of proteins, including the motivations for the project, the progress so far and directions for future work.