Probing amyloid fibril formation of the NFGAIL peptide by computer simulations

摘要

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.