Helix-to-sheet transition of the Aβ42 peptide revealed using an enhanced sampling strategy and Markov state model.

ABSTRACT: The self-assembly of Aβ peptides into toxic oligomers and fibrils is the primary cause of Alzheimer's disease. Moreover, the conformational transition from helix to sheet is considered a crucial step in the aggregation of Aβ peptides. However, the structural details of this process still remain unclear due to the heterogeneity and transient nature of the Aβ peptides. In this study, we developed an enhanced sampling strategy that combines artificial neural networks (ANN) with metadynamics to explore the conformational space of the Aβ42 peptides. The strategy consists of two parts: applying ANN to optimize CVs and conducting metadynamics based on the resulting CVs to sample conformations. The results showed that this strategy achieved better sampling performance in terms of the distribution

SUBMITTER: Wen H 

PROVIDER: S-EPMC10825278 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature