Insights into structure, stability, and toxicity of monomeric and aggregated polyglutamine models from molecular dynamics simulations.

ABSTRACT: Nine genetically inherited neurodegenerative diseases are linked to abnormal expansions of a polyglutamine (polyQ) encoding region. Over the years, several structural models for polyQ regions have been proposed and confuted. The cross-beta-spine steric zipper motif, identified recently for the GNNQQNY peptide, represents an attractive model for amyloid fibers formed by polyQ fragments. Here we report a detailed molecular dynamics investigation of polyQ models assembled by cross-beta-spine steric zipper motifs. Our simulations indicate clearly that these assemblies are very stable. Glutamine side chains contribute strongly to the overall stability of the models by fitting perfectly within the zipper. In contrast to GNNQQNY zipper motifs, hydrogen bonding interactions provide a significant c

SUBMITTER: Esposito L 

PROVIDER: S-EPMC2367175 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature