Journal of Anesthesia & Clinical Research
Open Access

Human μ Opioid Receptor Models with Evaluation of the Accuracy Using the Crystal Structure of the Murine μ Opioid Receptor

Jose Manuel Perez-Aguilar¹, Jeffery G. Saven^1* and Renyu Liu^2*

¹Department of Chemistry, University of Pennsylvania, Philadelphia, 19104, USA

²Department of Anesthesiology and Critical Care, Hospital of University of Pennsylvania, Philadelphia, 19104, USA

*Corresponding Authors:

Jeffery G. Saven
Department of Chemistry, University of Pennsylvania
231 South 34th Street, Philadelphia, PA 19104 USA
Tel: 215-573-6062
Fax: 215-573-6416
E-mail: [email protected]

Renyu Liu, MD, Ph.D
Assistant Professor, Department of Anesthesiology and Critical Care
Perelman School of Medicine at the University of Pennsylvania
336 John Morgan building,3620 Hamilton Walk, Philadelphia, PA 19104
Tel: 2156623750
Fax: 2153495078
E-mail: [email protected]

Received Date: June 25, 2012; Accepted Date: June 30, 2012; Published Date: July 02, 2012

Citation: Perez-Aguilar JM, Saven JG, Liu R (2012) Human µ Opioid Receptor Models with Evaluation of the Accuracy Using the Crystal Structure of the Murine µ Opioid Receptor. J Anesth Clin Res 3:218 doi: 10.4172/2155-6148.1000218

Copyright: © 2012 Perez-Aguilar JM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

To read the full article Peer-reviewed Article PDF | Peer-reviewed Full Article

Models of the human μ opioid receptor were constructed using G-protein-coupled receptor (GPCR) structures and homology (comparative) modeling techniques. The recent publication of a high-resolution crystal structure of a construct based on the murine μ opioid receptor offers a unique opportunity to evaluate the reliability of the homology models and test the relevance of introducing more templates (known structures) to increase the accuracy of the comparative models. In the first model two templates were used: the β₂ adrenergic and bovine rhodopsin receptors. For the second model, four templates were utilized: the β₂ adrenergic, bovine rhodopsin, β₁ adrenergic, and A_2A adenosine receptors. Including additional templates improved the accuracy of structural motifs and other features of the model when the same sequence alignment was used. The predicted structures were especially relevant in important receptor regions such as the DRY motif, which has been associated with receptor activation. Additionally, this study showed that receptor sequence similarity is crucial in homology modeling, as indicated in the case of the highly diverse EC2 loop. This study demonstrates the reliability of the homology modeling technique in the case of the μ opioid receptor, a member of the rhodopsin-like family class of GPCRs. The addition of more templates improved the accuracy of the model. The findings regarding the modeling has significant implication to other GPCRs where the crystal structure is still unknown and suggest that homology modeling techniques can provide high quality structural models for interpreting experimental findings and formulating structurally based hypotheses regarding the activity of these important receptors.