title: In silico assembly of Alzheimer's Abeta16-22 peptide into beta-sheets.
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.
authors.affiliation: Contribution from the Information Génomique et Structurale, UPR 2589 CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Santini
authors.forename: Normand
authors.initials: N
authors.lastname: Mousseau
authors.forename: Philippe
authors.initials: P
authors.lastname: Derreumaux
mesh_terms: 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
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C417223:amyloid beta-protein (16-22)