Thermodynamics of the dimerization of amyloidogenic proteins : a computer simulation study using stochastic approximation Monte Carlo

Abstract

This thesis explores the dimerization of amyloidogenic proteins - polyglutamine, amyloid-beta (Aβ), and parathyroid hormone (PTH) - using computational methods to uncover key thermodynamic and structural properties. Simulations characterize phase transitions and molecular structures within distinct phases. For polyglutamine, the dependence of phase transition temperatures on chain length and aggregate formation is analyzed. Aβ(1-40) and Aβ(1-42) systems reveal structural and thermodynamic differences driving aggregation. PTH of various length is studied to assess chain length effects on dimerization and aggregation. A comparison between Aβ and PTH dimerization is conducted. The intermediate-resolution PRIME20 protein model and stochastic approximation Monte Carlo (SAMC) simulations are employed. This work advances understanding of the thermodynamic and structural principles underlying amyloid dimerization and aggregation.