Molecular dynamics simulations to investigate the stability and aggregation behaviour of the amyloid-forming peptide VQIVYK from tau protein

Jian Hua Zhao, Hsuan Liang Liu, Chih Kuang Chuang, Kung Tien Liu, Wei Bor Tsai, Yih Ho

研究成果: 雜誌貢獻文章同行評審

12 引文 斯高帕斯(Scopus)

摘要

The formation of paired helical filaments arising from the short hexapeptide in the third repeat of tau protein, 306VQIVYK 311, is critical for tau polymerisation. The atomic structure of the VQIVYK oligomer has revealed a dry, tightly self-complementing structure between theneighbouring β-sheet layers, termed as 'steric zipper'. In this study, several molecular dynamics simulations with all-atom explicit water were conducted to investigate the structural stability and aggregation behaviour of the VQIVYK peptide with various sizes and its single alanine replacement mutations. Our results indicate that the van der Waals interaction between side chains of Q2, the π-π stacking interaction between aromatic rings of Y5, and the electrostatic interaction between K6 and the C-terminus play an important role in stabilising the VQIVYK oligomers within the same β-sheet layer, while hydrophobic steric zipper involving V1, I3 and Y5 is responsible for holding the neighbouring β-sheet layers together. The twisted angles of the VQIVYK oligomers were also analysed and shown to be size dependent. The present results not only provide atomic insights into amyloid formation, but are also helpful for designing new or modified capping peptides and inhibitors to prevent fibril formation of the VQIVYK peptide from tau protein.

原文英語
頁(從 - 到)1013-1024
頁數12
期刊Molecular Simulation
36
發行號13
DOIs
出版狀態已發佈 - 十一月 2010

ASJC Scopus subject areas

  • 化學 (全部)
  • 資訊系統
  • 建模與模擬
  • 化學工程 (全部)
  • 材料科學(全部)
  • 凝聚態物理學

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