The intrinsic helical propensities of the helical fragments in prion protein under neutral and low pH conditions: A replica exchange molecular dynamics study

Xiaoliang Lu, Juan Zeng, Ya Gao, John Zhang, Dawei Zhang, Ye Mei

Research output: Contribution to journalArticle

Abstract

Replica exchange molecular dynamics simulations in neutral and acidic aqueous solutions were employed to study the intrinsic helical propensities of three helices in both Syrian hamster (syPrP) and human (huPrP) prion proteins. The helical propensities of syPrP HA and huPrP HA are very high under both pH conditions, which implies that HA is barely involved in the helix-to-β transition. The SyPrP HB chain has a strong tendency to adopt an extended conformation, which is possibly involved in the mechanism of infectious prion diseases in Syrian hamster. HuPrP HC has more of a preference for the extended conformation than huPrP HA and huPrP HB do, which leads to the conjecture that it is more likely to be the source of β-rich structure for human prion protein. We also noticed that the presence of salt bridges is not correlated with helical propensity, indicating that salt bridges do not stabilize helices.

Original languageEnglish (US)
Pages (from-to)4897-4908
Number of pages12
JournalJournal of Molecular Modeling
Volume19
Issue number11
DOIs
StatePublished - Nov 2013

Fingerprint

replicas
helices
Conformations
Molecular dynamics
hamsters
Salts
fragments
molecular dynamics
proteins
Prions
salts
Ion exchange
infectious diseases
Computer simulation
tendencies
aqueous solutions
simulation

Keywords

  • Helical propensity
  • pH condition
  • Prion
  • Replica exchange molecular dynamics

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Catalysis
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

The intrinsic helical propensities of the helical fragments in prion protein under neutral and low pH conditions : A replica exchange molecular dynamics study. / Lu, Xiaoliang; Zeng, Juan; Gao, Ya; Zhang, John; Zhang, Dawei; Mei, Ye.

In: Journal of Molecular Modeling, Vol. 19, No. 11, 11.2013, p. 4897-4908.

Research output: Contribution to journalArticle

@article{1083edcdf4264579a20a242bdef2caf8,
title = "The intrinsic helical propensities of the helical fragments in prion protein under neutral and low pH conditions: A replica exchange molecular dynamics study",
abstract = "Replica exchange molecular dynamics simulations in neutral and acidic aqueous solutions were employed to study the intrinsic helical propensities of three helices in both Syrian hamster (syPrP) and human (huPrP) prion proteins. The helical propensities of syPrP HA and huPrP HA are very high under both pH conditions, which implies that HA is barely involved in the helix-to-β transition. The SyPrP HB chain has a strong tendency to adopt an extended conformation, which is possibly involved in the mechanism of infectious prion diseases in Syrian hamster. HuPrP HC has more of a preference for the extended conformation than huPrP HA and huPrP HB do, which leads to the conjecture that it is more likely to be the source of β-rich structure for human prion protein. We also noticed that the presence of salt bridges is not correlated with helical propensity, indicating that salt bridges do not stabilize helices.",
keywords = "Helical propensity, pH condition, Prion, Replica exchange molecular dynamics",
author = "Xiaoliang Lu and Juan Zeng and Ya Gao and John Zhang and Dawei Zhang and Ye Mei",
year = "2013",
month = "11",
doi = "10.1007/s00894-013-1985-7",
language = "English (US)",
volume = "19",
pages = "4897--4908",
journal = "Journal of Molecular Modeling",
issn = "1610-2940",
publisher = "Springer Verlag",
number = "11",

}

TY - JOUR

T1 - The intrinsic helical propensities of the helical fragments in prion protein under neutral and low pH conditions

T2 - A replica exchange molecular dynamics study

AU - Lu, Xiaoliang

AU - Zeng, Juan

AU - Gao, Ya

AU - Zhang, John

AU - Zhang, Dawei

AU - Mei, Ye

PY - 2013/11

Y1 - 2013/11

N2 - Replica exchange molecular dynamics simulations in neutral and acidic aqueous solutions were employed to study the intrinsic helical propensities of three helices in both Syrian hamster (syPrP) and human (huPrP) prion proteins. The helical propensities of syPrP HA and huPrP HA are very high under both pH conditions, which implies that HA is barely involved in the helix-to-β transition. The SyPrP HB chain has a strong tendency to adopt an extended conformation, which is possibly involved in the mechanism of infectious prion diseases in Syrian hamster. HuPrP HC has more of a preference for the extended conformation than huPrP HA and huPrP HB do, which leads to the conjecture that it is more likely to be the source of β-rich structure for human prion protein. We also noticed that the presence of salt bridges is not correlated with helical propensity, indicating that salt bridges do not stabilize helices.

AB - Replica exchange molecular dynamics simulations in neutral and acidic aqueous solutions were employed to study the intrinsic helical propensities of three helices in both Syrian hamster (syPrP) and human (huPrP) prion proteins. The helical propensities of syPrP HA and huPrP HA are very high under both pH conditions, which implies that HA is barely involved in the helix-to-β transition. The SyPrP HB chain has a strong tendency to adopt an extended conformation, which is possibly involved in the mechanism of infectious prion diseases in Syrian hamster. HuPrP HC has more of a preference for the extended conformation than huPrP HA and huPrP HB do, which leads to the conjecture that it is more likely to be the source of β-rich structure for human prion protein. We also noticed that the presence of salt bridges is not correlated with helical propensity, indicating that salt bridges do not stabilize helices.

KW - Helical propensity

KW - pH condition

KW - Prion

KW - Replica exchange molecular dynamics

UR - http://www.scopus.com/inward/record.url?scp=84888286808&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888286808&partnerID=8YFLogxK

U2 - 10.1007/s00894-013-1985-7

DO - 10.1007/s00894-013-1985-7

M3 - Article

VL - 19

SP - 4897

EP - 4908

JO - Journal of Molecular Modeling

JF - Journal of Molecular Modeling

SN - 1610-2940

IS - 11

ER -