Structural stability and aggregation behavior of the VEALYL peptide derived from human insulin: a molecular dynamics simulation study.

Yeh Fon Lin, Jian Hua Zhao, Hsuan Liang Liu, Kung Tien Liu, Jenn Tzong Chen, Wei Bor Tsai, Yih Ho

研究成果: 雜誌貢獻文章同行評審

9 引文 斯高帕斯(Scopus)

摘要

The VEALYL peptide from B chain (residues 12-17) of insulin has been shown to form amyloid-like fibrils. Recently, the atomic structure of the VEALYL oligomer has been determined by X-ray microcrystallography and reveals a dry, tightly self-complementing structure between the neighboring beta-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 behavior of the VEALYL peptide with various sizes and its single glycine replacement mutations. The results of our single-layer models showed that the structural stability of the VEALYL oligomers increases significantly with increasing the number of beta-strands. We further suggested that the minimal nucleus seed for VEALYL fibril formation could be as small as three or four peptides. Our results also revealed that the hydrophobic interaction between E2 and Y5 plays an important role in stabilizing the adjacent beta-strands within the same layer, whereas the hydrophobic steric zipper formed via the side chains of V1, A3, L4, Y5, and L6 locks the two neighboring beta-sheet layers together. Mutation simulations showed that the substitution of a single glycine residue directly disrupts this steric zipper, resulting in the destabilization of the VEALYL oligomers. This study provides the atomic insights into understanding the aggregation behavior of the VEALYL peptide. It may also be helpful for designing new or modified capping peptides able to break the driving force for aggregation and to prevent the fibril formation of the VEALYL peptide and the insulin protein. (c) 2010 Wiley Periodicals, Inc.

原文英語
頁(從 - 到)269-278
頁數10
期刊Biopolymers
94
發行號3
DOIs
出版狀態已發佈 - 2010
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 生物物理學
  • 生物材料
  • 有機化學

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