Thermodynamic stabilities of amyloid fibrils remain mostly unknown due to experimental challenges. Here, we combine enhanced sampling methods to simulate all-atom models in explicit water in order to study the stability of nonpolar (Aβ16-21) and polar (IAPP28-33) fibrils. We find that the nonpolar fibril becomes more stable with increasing temperature, and its stability is dominated by entropy. In contrast, the polar fibril becomes less stable with increasing temperature, while it is stabilized by enthalpy. Our results show that the nature of side chains in the dry core of amyloid fibrils plays a dominant role in accounting for their thermodynamic stability.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Chemical Theory and Computation|
|State||Published - Jun 11 2019|
ASJC Scopus subject areas
- Computer Science Applications
- Physical and Theoretical Chemistry