In silico assembly of Alzheimer's Abeta16-22 peptide into beta-sheets.
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.
Santini
Sébastien
S
Contribution from the Information Génomique et Structurale, UPR 2589 CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
Mousseau
Normand
N
Derreumaux
Philippe
P
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C417223:amyloid beta-protein (16-22)