The possible structural models for polyglutamine aggregation: A molecular dynamics simulations study

Zheng Li Zhou, Jian Hua Zhao, Hsuan Liang Liu, Josephine W. Wu, Kung Tien Liu, Chih Kuang Chuang, Wei Bor Tsai, Yih Ho

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Huntington's disease is a neurodegenerative disorder caused by a polyglutamine (polyQ) expansion near the N-terminus of huntingtin. Previous studies have suggested that polyQ aggregation occurs only when the number of glutamine (Q) residues is more than 36-40, the disease threshold. However, the structural characteristics of polyQ nucleation in the very early stage of aggregation still remain elusive. In this study, we designed 18 simulation trials to determine the possible structural models for polyQ nucleation and aggregation with various shapes and sizes of initial β-helical structures, such as left-handed circular, right-handed rectangular, and left- and right-handed triangular. Our results show that the stability of these models significantly increases with increasing the number of rungs, while it is rather insensitive to the number of Qs in each rung. In particular, the 3-rung β-helical models are stable when they adopt the left-handed triangular and right-handed rectangular conformations due to the fact that they preserve high β-turn and β-sheet contents, respectively, during the simulation courses. Thus, we suggested that these two stable β-helical structures with at least 3 rungs might serve as the possible nucleation seeds for polyQ depending on how the structural elements of β-turn and β-sheet are sampled and preserved during the very early stage of aggregation.

Original languageEnglish
Pages (from-to)743-758
Number of pages16
JournalJournal of Biomolecular Structure and Dynamics
Issue number5
Publication statusPublished - Apr 2011


  • β-helix
  • Aggregation
  • Huntington's disease
  • Molecular dynamics simulations
  • Nucleation
  • Polyglutamine (polyQ)

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology


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