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 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

Fingerprint

Oligomerization
Molecular dynamics
PrPSc Proteins
Neurodegenerative diseases
molecular dynamics
proteins
Dimerization
Prions
Computer simulation
dimerization
Dimers
Agglomeration
simulation
dimers
Atoms
causes
atoms

ASJC Scopus subject areas

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

Cite this

Comparison of the unfolding and oligomerization of human prion protein under acidic and neutral environments by molecular dynamics simulations. / Gao, Ya; Zhu, Tong; Zhang, Chaomin; Zhang, John; Mei, Ye.

In: Chemical Physics Letters, Vol. 706, 16.08.2018, p. 594-600.

Research output: Contribution to journalArticle

@article{7c638560d15d4cc4ade81f6cbafa0900,
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 John Zhang and Ye Mei",
year = "2018",
month = "8",
day = "16",
doi = "10.1016/j.cplett.2018.07.014",
language = "English (US)",
volume = "706",
pages = "594--600",
journal = "Chemical Physics Letters",
issn = "0009-2614",
publisher = "Elsevier",

}

TY - JOUR

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85049756058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049756058&partnerID=8YFLogxK

U2 - 10.1016/j.cplett.2018.07.014

DO - 10.1016/j.cplett.2018.07.014

M3 - Article

VL - 706

SP - 594

EP - 600

JO - Chemical Physics Letters

JF - Chemical Physics Letters

SN - 0009-2614

ER -