Quantifying the parameters of Prusiner's heterodimer model for prion replication

Abstract

A novel approach for the determination of parameters in prion replication kinetics is developed based on Prusiner's heterodimer model. It is proposed to employ a simple 2D HP lattice model and a two-state transition theory to determine kinetic parameters that play the key role in the prion replication process. The simulation results reveal the most important facts observed in the prion diseases, including the long incubation time, rapid death following symptom manifestation, the effect of inoculation size, different mechanisms of the familial and infectious prion diseases, etc. Extensive simulation with various thermodynamic parameters shows that the Prusiner's heterodimer model is applicable, and the putative protein X plays a critical role in replication of the prion disease. © 2004 Elsevier B.V. All rights reserved.