Homogeneous and heterogeneous tertiary structure ensembles of amyloid-? peptides.

ABSTRACT: The interplay of modern molecular simulation and high-quality nuclear magnetic resonance (NMR) experiments has reached a fruitful stage for quantitative characterization of structural ensembles of disordered peptides. Amyloid-? 1-42 (A?42), the primary peptide associated with Alzheimer's disease, and fragments such as A?21-30 are both classified as intrinsically disordered peptides (IDPs). We use a variety of NMR observables to validate de novo molecular dynamics simulations in explicit water to characterize the tertiary structure ensemble of A?42 and A?21-30 from the perspective of their classification as IDPs. Unlike the A?21-30 fragment that conforms to expectations of an IDP that is primarily extended, we find that A?42 samples conformations reflecting all possible secondary structure categories and spans the range of IDP classifications from collapsed structured states to highly extended conformations, making it an IDP with a far more heterogeneous tertiary ensemble.

SUBMITTER: Ball KA 

PROVIDER: S-EPMC3474852 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature