In Silico Assembly of Alzheimer's Aβ16-22 Peptide into β-Sheets
- 26 August 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 126 (37) , 11509-11516
- https://doi.org/10.1021/ja047286i
Abstract
Recent studies suggest that soluble oligomers of amyloid-forming peptides have toxic effects in cell cultures. In this study, the folding of three Alzheimer's A beta(16-22) peptides have been simulated with the activation-relaxation technique and a generic energy model. Starting from randomly chosen states, the predicted lowest energy structure superposes within 1 A rms deviation from its conformation within the fibrils. This antiparallel structure is found to be in equilibrium with several out-of-register antiparallel beta-sheets and mixed parallel-antiparallel beta-sheets, indicating that full structural order in the fibrils requires larger aggregates. Folding involves the formation of dimers followed by the addition of a monomer and proceeds through a generalized mechanism between disordered and native alignments of beta-strands.Keywords
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