MELD-accelerated molecular dynamics help determine amyloid fibril structures.

ABSTRACT: It is challenging to determine the structures of protein fibrils such as amyloids. In principle, Molecular Dynamics (MD) modeling can aid experiments, but normal MD has been impractical for these large multi-molecules. Here, we show that MELD accelerated MD (MELD x MD) can give amyloid structures from limited data. Five long-chain fibril structures are accurately predicted from NMR and Solid State NMR (SSNMR) data. Ten short-chain fibril structures are accurately predicted from more limited restraints information derived from the knowledge of strand directions. Although the present study only tests against structure predictions - which are the most detailed form of validation currently available - the main promise of this physical approach is ultimately in going beyond structures to also g

SUBMITTER: Sharma B 

PROVIDER: S-EPMC8342454 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature