State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, China.
PLoS One. 2012;7(5):e36382. doi: 10.1371/journal.pone.0036382. Epub 2012 May 10.
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.
淀粉样纤维存在于许多致命的神经退行性疾病中，如阿尔茨海默病、帕金森病、2 型糖尿病和朊病毒病。胰岛素的 VEALYL 短肽已被证实会聚集类似淀粉样的纤维。然而，淀粉样纤维的聚集机制还不清楚。在这里，我们利用分子动力学模拟来分析 VEALYL 六聚体的稳定性。统计结果表明，疏水性残基在稳定 VEALYL 六聚体中起着关键作用。单点和两点突变体证实，VEALYL 的 Val1、Leu4 和 Tyr5 是关键残基。VEALYL 低聚物结果的一致性表明，中间状态可能是三聚体（3-0）和五聚体（3-2）。这些结果可以帮助我们深入了解淀粉样纤维的聚集机制。这些方法可用于研究其他短肽的淀粉样纤维的稳定性。
