Pre-oligomerisation stochastic dynamics of prions driven by water molecules

Abstract

Prions are proteinaceous infectious particles that cause neurodegenerative diseases in humans and animals. The complex nature of prions, with respect to their conformations and aggregations, has been an important area of research for quite some time. Here, we develop a model of prion dynamics prior to the formation of oligomers and subsequent development of prion diseases within a stochastic framework, based on the analytical Master Equation and Stochastic Simulation Algorithm by Gillespie. The results that we obtain shows that solvent water molecules act as driving agents in the dynamics of prion aggregation. Further, it is found that aggregated and non-aggregated proteins tend to co-exist in an equilibrium state, depending upon the reaction rate constants. These results may provide a theoretical and qualitative contexts of possible therapeutic strategies in the treatment of prion diseases.