Analysis of Dissociation Pathway of HET-s Prion Using Steered Pulling Simulation

Prion is a group of the proteins known for its infection mechanisms of Creutzfeldt-Jakob disease (CJD) and other diseases. Solved structures and proven biological roles of fungal prions add tremendous potential to conducting computational simulations. Our research focuses on the binding dynamics of HET-s(218-289), one of the heterokaryon fungal prion originated from Podospora anserina, by calculating the binding free energy using umbrella sampling at 300 K. The binding free energy calculated was $-54.5kcal\;mol^{-1}$, relatively similar to the binding energy of other amyloid fibrils. The simulation result suggests the thermodynamic properties of ${\beta}$-solenoid of HET-s prion and its similarity in dissociation pathways compared to amyloids.