Mapping conformational ensembles of a? oligomers in molecular dynamics simulations.

ABSTRACT: Although the oligomers formed by A? peptides appear to be the primary cytotoxic species in Alzheimer's disease, detailed information about their structures appears to be lacking. In this article, we use exhaustive replica exchange molecular dynamics and an implicit solvent united-atom model to study the structural properties of A? monomers, dimers, and tetramers. Our analysis suggests that the conformational ensembles of A? dimers and tetramers are very similar, but sharply distinct from those sampled by the monomers. The key conformational difference between monomers and oligomers is the formation of ?-structure in the oligomers occurring together with the loss of intrapeptide interactions and helix structure. Our simulations indicate that, independent of oligomer order, the A? aggregation interface is largely confined to the sequence region 10-23, which forms the bulk of interpeptide interactions. We show that the fractions of ? structure computed in our simulations and measured experimentally are in good agreement.

SUBMITTER: Kim S 

PROVIDER: S-EPMC2941018 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature