Computer simulation model for aggregration in a multi protein model system

Protein misfolding and aggregation is believed to be associated with diseases such as Alzheimer’s Disease, Huntington’s Disease, ALS and others. Healthy proteins typically function in their folded collapsed structure (native state) but in certain cases they unfold into strands and beta sheets, which then aggregate into larger fibrils and plaques. To analyze this behaviour, we have developed a computer simulation model using discontinuous molecular dynamics on a system of Trp cage proteins. The Trp cage is a small (20 residue, 189 atoms) protein known to fold quickly and therefore is suitable for computer simulation. Previous work (Linhananta, Boer, Mackay J Chem Phys 122, 114901. 2005) modeled the Trp Cage with the all atom Go model for atom-atom pair interaction potential within a single protein. We expand on this previous work by incorporating the Go potential for atom-atom pairs between separate proteins. We observe destabilization and unfolding due to perturbation by neighbouring proteins and analyze the aggregation behaviour at various concentrations and temperatures. Transition state analysis shows the folding/unfolding transition is less cooperative than for the single protein system.