title: Insight into the stability of cross-β amyloid fibril from VEALYL short peptide with molecular dynamics simulation.
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.
authors.affiliation: State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Qingfen
authors.initials: Q
authors.lastname: Yu
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Chen
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017354:Point Mutation; D055550:Protein Stability
chemical_list: D000682:Amyloid; D007328:Insulin; D010455:Peptides