Abstract
Amyloid fibrils are found in many fatal neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, type II diabetes, and prion disease. The VEALYL short peptide from insulin has been confirmed to aggregate amyloid-like fibrils. However, the aggregation mechanism of amyloid fibril is poorly understood. Here, we utilized molecular dynamics simulation to analyse the stability of VEALYL hexamer. The statistical results indicate that hydrophobic residues play key roles in stabilizing VEALYL hexamer. Single point and two linkage mutants confirmed that Val1, Leu4, and Tyr5 of VEALYL are key residues. The consistency of the results for the VEALYL oligomer suggests that the intermediate states might be trimer (3-0) and pentamer(3-2). These results can help us to obtain an insight into the aggregation mechanism of amyloid fibril. These methods can be used to study the stability of amyloid fibril from other short peptides.