Oligomerization of amyloid Abeta16-22 peptides using hydrogen bonds and hydrophobicity forces.
The 16-22 amino-acid fragment of the beta-amyloid peptide associated with the Alzheimer's disease, Abeta, is capable of forming amyloid fibrils. Here we study the aggregation mechanism of Abeta16-22 peptides by unbiased thermodynamic simulations at the atomic level for systems of one, three, and six Abeta16-22 peptides. We find that the isolated Abeta16-22 peptide is mainly a random coil in the sense that both the alpha-helix and beta-strand contents are low, whereas the three- and six-chain systems form aggregated structures with a high beta-sheet content. Furthermore, in agreement with experiments on Abeta16-22 fibrils, we find that large parallel beta-sheets are unlikely to form. For the six-chain system, the aggregated structures can have many different shapes, but certain particularly stable shapes can be identified.
Favrin
Giorgio
G
Complex Systems Division, Department of Theoretical Physics, Lund University, Lund, Sweden.
Irbäck
Anders
A
Mohanty
Sandipan
S
D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D019281:Dimerization; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000032:analysis / Q000737:chemistry; D010446:Peptide Fragments / Q000032:analysis* / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013314:Stress, Mechanical; D013696:Temperature
D016229:Amyloid beta-Peptides; D046912:Multiprotein Complexes; D010446:Peptide Fragments; C417223:amyloid beta-protein (16-22)