Next Article in Journal
Identification of Major Degradation Products of Ketoconazole
Previous Article in Journal
Scavenger Activity Evaluation of the Clove Bud Essential Oil (Eugenia caryophyllus) and Eugenol Derivatives Employing ABTS+• Decolorization
Article Menu

Article Versions

Export Article

Open AccessArticle
Sci. Pharm. 2011, 79(4), 793-816; doi:10.3797/scipharm.1106-24

Prediction of the Human EP1 Receptor Binding Site by Homology Modeling and Molecular Dynamics Simulation

1
Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2
Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
3
School of Pharmacy and Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4
Department of Pharmacology, Firoozgar Hospital, Clinical Research Development Center, Tehran, Iran
*
Author to whom correspondence should be addressed.
Received: 28 June 2011 / Accepted: 7 August 2011 / Published: 7 August 2011
Download PDF [1103 KB, uploaded 28 September 2016]

Abstract

The prostanoid receptor EP1 is a G-protein-coupled receptor (GPCR) known to be involved in a variety of pathological disorders such as pain, fever and inflammation. These receptors are important drug targets, but design of subtype specific agonists and antagonists has been partially hampered by the absence of three-dimensional structures for these receptors. To understand the molecular interactions of the PGE2, an endogen ligand, with the EP1 receptor, a homology model of the human EP1 receptor (hEP1R) with all connecting loops was constructed from the 2.6 Å resolution crystal structure (PDB code: 1L9H) of bovine rhodopsin. The initial model generated by MODELLER was subjected to molecular dynamics simulation to assess quality of the model. Also, a step by step ligand-supported model refinement was performed, including initial docking of PGE2 and iloprost in the putative binding site, followed by several rounds of energy minimizations and molecular dynamics simulations. Docking studies were performed for PGE2 and some other related compounds in the active site of the final hEP1 receptor model. The docking enabled us to identify key molecular interactions supported by the mutagenesis data. Also, the correlation of r2=0.81 was observed between the Ki values and the docking scores of 15 prostanoid compounds. The results obtained in this study may provide new insights toward understanding the active site Sci Pharm. 2011; 79: 793–816 conformation of the hEP1 receptor and can be used for the structure-based design of novel specific ligands.
Keywords: Homology modeling; G-protein coupled receptors (GPCR); Human prostanoid E1 receptor; Flexible-ligand docking; Molecular dynamics simulation Homology modeling; G-protein coupled receptors (GPCR); Human prostanoid E1 receptor; Flexible-ligand docking; Molecular dynamics simulation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

ZARE, B.; MADADKAR-SOBHANI, A.; DASTMALCHI, S.; MAHMOUDIAN, M. Prediction of the Human EP1 Receptor Binding Site by Homology Modeling and Molecular Dynamics Simulation. Sci. Pharm. 2011, 79, 793-816.

Show more citation formats Show less citations formats

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Sci. Pharm. EISSN 2218-0532 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top