Title
Homogeneous and Heterogeneous Tertiary Structure Ensembles of Amyloid-β Peptides
Document Type
Article
Publication Date
2011
Published In
Biochemistry
Volume
50
Issue
35
Pages
7612-7628
DOI
10.1021/bi200732x
Recommended Citation
K. Aurelia Ball, Aaron H. Phillips, Paul S. Nerenberg, Nicolas L. Fawzi, David E. Wemmer, Teresa Head-Gordon. Homogeneous and Heterogeneous Tertiary Structure Ensembles of Amyloid-b Peptides. Biochemistry, 2011; 50:7612-7628.
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-β 1–42 (Aβ42), the primary peptide associated with Alzheimer’s disease, and fragments such as Aβ21–30 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 Aβ42 and Aβ21–30 from the perspective of their classification as IDPs. Unlike the Aβ21–30 fragment that conforms to expectations of an IDP that is primarily extended, we find that Aβ42 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.