Conformational analysis of endomorphin-1 by molecular dynamics methods

B. Leitgeb, A. Szekeres, G. Tóth

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Endomorphin-1 (EM1, H-Tyr-Pro-Trp-Phe-NH2) is a highly potent and selective agonist for the μ-opioid receptor. A conformational analysis of this tetrapeptide was carried out by simulated annealing and molecular dynamics methods. EM1 was modeled in the neutral (NH2-) and cationic (NH3+-) forms of the N-terminal amino group. The results of NMR measurements were utilized to perform simulations with restrained cis and trans Tyr1-Pro2 peptide bonds. Preferred conformational regions in the Φ22, Φ 33 and Φ44 Ramachandran plots were identified. The g(+), g(-) and trans rotamer populations of the side-chains of the Tyr1, Trp3 and Phe4 residues were determined in χ1 space. The distances between the N-terminal N atom and the other backbone N and O atoms, and the distances between the centers of the aromatic side-chain rings and the Pro2 ring were measured. The preferred secondary structures were determined as different types of β-turns and γ-turns. In the conformers of trans-EM1, an inverse γ-turn can be formed in the N-terminal region, but in the conformers of cis-EM1 the N-terminal inverse γ-turn is absent. Regular and inverse γ-turns were observed in the C-terminal region in both isomers. These β- and γ-turns were stabilized by intramolecular H-bonds and bifurcated H-bonds.

Original languageEnglish
Pages (from-to)145-157
Number of pages13
JournalJournal of Peptide Research
Volume62
Issue number4
DOIs
Publication statusPublished - Oct 1 2003

Fingerprint

Opioid Receptors
Molecular Dynamics Simulation
Molecular dynamics
Atoms
Peptides
Simulated annealing
Isomers
Population
Nuclear magnetic resonance
endomorphin 1

Keywords

  • β-turns
  • Bifurcation and inverse bifurcation
  • C-terminal γ-turns and inverse γ-turns
  • Conformational analysis
  • Endomorphin-1
  • Intramolecular H-bonds
  • Molecular dynamics
  • N-terminal inverse γ-turns
  • Simulated annealing

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Conformational analysis of endomorphin-1 by molecular dynamics methods. / Leitgeb, B.; Szekeres, A.; Tóth, G.

In: Journal of Peptide Research, Vol. 62, No. 4, 01.10.2003, p. 145-157.

Research output: Contribution to journalArticle

@article{4e51100a4b804284963deb95bf34d457,
title = "Conformational analysis of endomorphin-1 by molecular dynamics methods",
abstract = "Endomorphin-1 (EM1, H-Tyr-Pro-Trp-Phe-NH2) is a highly potent and selective agonist for the μ-opioid receptor. A conformational analysis of this tetrapeptide was carried out by simulated annealing and molecular dynamics methods. EM1 was modeled in the neutral (NH2-) and cationic (NH3+-) forms of the N-terminal amino group. The results of NMR measurements were utilized to perform simulations with restrained cis and trans Tyr1-Pro2 peptide bonds. Preferred conformational regions in the Φ2-Ψ2, Φ 3-Ψ3 and Φ4-Ψ4 Ramachandran plots were identified. The g(+), g(-) and trans rotamer populations of the side-chains of the Tyr1, Trp3 and Phe4 residues were determined in χ1 space. The distances between the N-terminal N atom and the other backbone N and O atoms, and the distances between the centers of the aromatic side-chain rings and the Pro2 ring were measured. The preferred secondary structures were determined as different types of β-turns and γ-turns. In the conformers of trans-EM1, an inverse γ-turn can be formed in the N-terminal region, but in the conformers of cis-EM1 the N-terminal inverse γ-turn is absent. Regular and inverse γ-turns were observed in the C-terminal region in both isomers. These β- and γ-turns were stabilized by intramolecular H-bonds and bifurcated H-bonds.",
keywords = "β-turns, Bifurcation and inverse bifurcation, C-terminal γ-turns and inverse γ-turns, Conformational analysis, Endomorphin-1, Intramolecular H-bonds, Molecular dynamics, N-terminal inverse γ-turns, Simulated annealing",
author = "B. Leitgeb and A. Szekeres and G. T{\'o}th",
year = "2003",
month = "10",
day = "1",
doi = "10.1034/j.1399-3011.2003.00084.x",
language = "English",
volume = "62",
pages = "145--157",
journal = "Chemical Biology and Drug Design",
issn = "1747-0277",
publisher = "Blackwell",
number = "4",

}

TY - JOUR

T1 - Conformational analysis of endomorphin-1 by molecular dynamics methods

AU - Leitgeb, B.

AU - Szekeres, A.

AU - Tóth, G.

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Endomorphin-1 (EM1, H-Tyr-Pro-Trp-Phe-NH2) is a highly potent and selective agonist for the μ-opioid receptor. A conformational analysis of this tetrapeptide was carried out by simulated annealing and molecular dynamics methods. EM1 was modeled in the neutral (NH2-) and cationic (NH3+-) forms of the N-terminal amino group. The results of NMR measurements were utilized to perform simulations with restrained cis and trans Tyr1-Pro2 peptide bonds. Preferred conformational regions in the Φ2-Ψ2, Φ 3-Ψ3 and Φ4-Ψ4 Ramachandran plots were identified. The g(+), g(-) and trans rotamer populations of the side-chains of the Tyr1, Trp3 and Phe4 residues were determined in χ1 space. The distances between the N-terminal N atom and the other backbone N and O atoms, and the distances between the centers of the aromatic side-chain rings and the Pro2 ring were measured. The preferred secondary structures were determined as different types of β-turns and γ-turns. In the conformers of trans-EM1, an inverse γ-turn can be formed in the N-terminal region, but in the conformers of cis-EM1 the N-terminal inverse γ-turn is absent. Regular and inverse γ-turns were observed in the C-terminal region in both isomers. These β- and γ-turns were stabilized by intramolecular H-bonds and bifurcated H-bonds.

AB - Endomorphin-1 (EM1, H-Tyr-Pro-Trp-Phe-NH2) is a highly potent and selective agonist for the μ-opioid receptor. A conformational analysis of this tetrapeptide was carried out by simulated annealing and molecular dynamics methods. EM1 was modeled in the neutral (NH2-) and cationic (NH3+-) forms of the N-terminal amino group. The results of NMR measurements were utilized to perform simulations with restrained cis and trans Tyr1-Pro2 peptide bonds. Preferred conformational regions in the Φ2-Ψ2, Φ 3-Ψ3 and Φ4-Ψ4 Ramachandran plots were identified. The g(+), g(-) and trans rotamer populations of the side-chains of the Tyr1, Trp3 and Phe4 residues were determined in χ1 space. The distances between the N-terminal N atom and the other backbone N and O atoms, and the distances between the centers of the aromatic side-chain rings and the Pro2 ring were measured. The preferred secondary structures were determined as different types of β-turns and γ-turns. In the conformers of trans-EM1, an inverse γ-turn can be formed in the N-terminal region, but in the conformers of cis-EM1 the N-terminal inverse γ-turn is absent. Regular and inverse γ-turns were observed in the C-terminal region in both isomers. These β- and γ-turns were stabilized by intramolecular H-bonds and bifurcated H-bonds.

KW - β-turns

KW - Bifurcation and inverse bifurcation

KW - C-terminal γ-turns and inverse γ-turns

KW - Conformational analysis

KW - Endomorphin-1

KW - Intramolecular H-bonds

KW - Molecular dynamics

KW - N-terminal inverse γ-turns

KW - Simulated annealing

UR - http://www.scopus.com/inward/record.url?scp=0141504412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141504412&partnerID=8YFLogxK

U2 - 10.1034/j.1399-3011.2003.00084.x

DO - 10.1034/j.1399-3011.2003.00084.x

M3 - Article

C2 - 12969194

AN - SCOPUS:0141504412

VL - 62

SP - 145

EP - 157

JO - Chemical Biology and Drug Design

JF - Chemical Biology and Drug Design

SN - 1747-0277

IS - 4

ER -