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

doi:10.1016/j.cplett.2018.07.014

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

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Aggregation of the misfolded scrapie prion protein (PrP^Sc) is known to cause neurodegenerative diseases. In this paper, we have investigated the stability of PrP^C by combining coarse-grained model and all-atom molecular simulations. Our results show that the unfolding of PrP^C 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 language	English (US)
Pages (from-to)	594-600
Number of pages	7
Journal	Chemical Physics Letters
Volume	706
DOIs	https://doi.org/10.1016/j.cplett.2018.07.014
State	Published - Aug 16 2018

ASJC Scopus subject areas

General Physics and Astronomy
Physical and Theoretical Chemistry

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10.1016/j.cplett.2018.07.014

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

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.",

author = "Ya Gao and Tong Zhu and Chaomin Zhang and Zhang, {John Z.H.} and Ye Mei",

note = "Publisher Copyright: {\textcopyright} 2018",

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doi = "10.1016/j.cplett.2018.07.014",

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T1 - Comparison of the unfolding and oligomerization of human prion protein under acidic and neutral environments by molecular dynamics simulations

AU - Gao, Ya

AU - Zhu, Tong

AU - Zhang, Chaomin

AU - Zhang, John Z.H.

AU - Mei, Ye

PY - 2018/8/16

Y1 - 2018/8/16

N2 - 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.

AB - 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.

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JO - Chemical Physics Letters

JF - Chemical Physics Letters

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

Abstract

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