Probing amyloid fibril formation of the NFGAIL peptide by computer simulations.
Amyloid fibril formation, as observed in Alzheimer's disease and type II diabetes, is currently described by a nucleation-condensation mechanism, but the details of the process preceding the formation of the nucleus are still lacking. In this study, using an activation-relaxation technique coupled to a generic energy model, we explore the aggregation pathways of 12 chains of the hexapeptide NFGAIL. The simulations show, starting from a preformed parallel dimer and ten disordered chains, that the peptides form essentially amorphous oligomers or more rarely ordered beta-sheet structures where the peptides adopt a parallel orientation within the sheets. Comparison between the simulations indicates that a dimer is not a sufficient seed for avoiding amorphous aggregates and that there is a critical threshold in the number of connections between the chains above which exploration of amorphous aggregates is preferred.
Melquiond
Adrien
A
Laboratoire de Biochimie Théorique, UPR 9080 CNRS, Institut de Biologie Physico-Chimique et Université Paris 7, 13 rue Pierre et Marie Curie, 75005 Paris, France.
Gelly
Jean-Christophe
JC
Mousseau
Normand
N
Derreumaux
Philippe
P
D000682:Amyloid / Q000737:chemistry*; D003198:Computer Simulation; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
D000682:Amyloid; D010455:Peptides