Kinetics and mechanical stability of the fibril state control fibril formation time of polypeptide chains: A computational study.

ABSTRACT: Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite much progress in the understanding of the protein aggregation process, the factors governing fibril formation rates and fibril stability have not been fully understood. Using lattice models, we have shown that the fibril formation time is controlled by the kinetic stability of the fibril state but not by its energy. Having performed all-atom explicit solvent molecular dynamics simulations with the GROMOS43a1 force field for full-length amyloid beta peptides Aβ₄₀ and Aβ₄₂ and truncated peptides, we demonstrated that kinetic stability can be accessed via mechanical stability in such a way that the hi

SUBMITTER: Kouza M 

PROVIDER: S-EPMC5991969 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature