Premium
Conformational analysis of endomorphin‐2 by molecular dynamics methods
Author(s) -
Leitgeb Balázs,
Ötvös Ferenc,
Tóth Géza
Publication year - 2003
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.10333
Subject(s) - chemistry , ramachandran plot , intramolecular force , molecular dynamics , stereochemistry , crystallography , molecule , peptide , hydrogen bond , side chain , protein structure , computational chemistry , biochemistry , organic chemistry , polymer
Endomorphin‐2 (EM2, H–Tyr–Pro–Phe–Phe–NH 2 ) is a highly potent and selective μ‐opioid receptor agonist. A conformational analysis of EM2 was carried out by simulated annealing (SA) and molecular dynamics (MD) methods. Molecular modeling was conducted on both neutral (N‐terminal NH 2 ) and charged (N‐terminal NH 3 + ) molecules. Based on the results of NMR investigations showing an equilibrium mixture of cis and trans Tyr 1 –Pro 2 peptide bonds for EM2 in solution, simulations were performed with restrained cis ‐Pro and trans ‐Pro peptide bonds, too. A separate SA study with unrestrained Pro peptide bonds was also conducted. Preferred conformational states are presented in Ramachandran plots. The g (+), g (‐), and trans populations of the aromatic amino acid residue side chains were determined in χ 1 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 rings and the Pro 2 ring, were determined. The energy distribution of the structures obtained by SA was calculated. The preferred secondary structural elements were different kinds of β‐turns, an inverse γ‐turn located in the N‐terminal region, and regular and inverse γ‐turns located in the C‐terminal region. These turns were stabilized by intramolecular H‐bonds and bifurcated H‐bonds. © 2003 Wiley Periodicals, Inc. Biopolymers 68: 497–511, 2003