Kinetic control of dimer structure formation in amyloid fibrillogenesis.

ABSTRACT: Amyloid fibril formation involves nonfibrillar oligomeric intermediates, which are important as possible cytotoxic species in neurodegenerative diseases. However, their transient nature and polydispersity have made it difficult to identify their formation mechanism or structure. We have investigated the dimerization process, the first step in aggregate formation, by multiple molecular dynamics simulations of five beta-sheet-forming peptides. Contrary to the regular beta-sheet structure of the amyloid fibril, the dimers exhibit all possible combinations of beta-sheets, with an overall preference for antiparallel arrangements. Through statistical analysis of 1,000 dimerization trajectories, each 1 ns in length, we have demonstrated that the observed distribution of dimer configurations is ki

SUBMITTER: Hwang W 

PROVIDER: S-EPMC516495 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature