Comparison of the unfolding and oligomerization of human prion protein under acidic and neutral environments by molecular dynamics simulations

Ya Gao, Tong Zhu, Chaomin Zhang, John Z.H. Zhang, Ye Mei

Research output: Contribution to journalArticle

Abstract

Aggregation of the misfolded scrapie prion protein (PrPSc) is known to cause neurodegenerative diseases. In this paper, we have investigated the stability of PrPC by combining coarse-grained model and all-atom molecular simulations. Our results show that the unfolding of PrPC starts from the opening of the folded domain with α1 moving away from α2α3 domain, and then arrives at a metastable intermediate, and forms a more stable dimer complex in the end. This work unravels the mechanism of the early stage of conformational conversion and dimerization of prion protein and provides significant hints for the development of anti-prion therapeutics.

Original languageEnglish (US)
Pages (from-to)594-600
Number of pages7
JournalChemical Physics Letters
Volume706
DOIs
StatePublished - Aug 16 2018

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ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry

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