Pre-oligomerisation stochastic dynamics of prions driven by water molecules

TL;DR

This paper models the early stochastic dynamics of prion aggregation, highlighting the role of water molecules as driving agents, and explores equilibrium states that could inform therapeutic strategies for prion diseases.

Contribution

It introduces a novel stochastic model of prion pre-oligomerisation dynamics driven by water molecules, using Master Equation and Gillespie algorithms.

Findings

Water molecules influence prion aggregation dynamics.

Aggregated and non-aggregated proteins coexist in equilibrium.

Reaction rates determine the balance between different protein states.

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.