HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) All Versions of this Article: ps.04720304v1 13/8/1997    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aburi, M. Articles by Smith, P. E. Search for Related Content PubMed PubMed Citation Articles by Aburi, M. Articles by Smith, P. E. Social Bookmarking                   What's this?

Modeling and simulation of the human opioid receptor

¹ Department of Biochemistry and
² Department of Chemistry, Kansas State University, Manhattan, Kansas 66506, USA

(RECEIVED March 4, 2004; FINAL REVISION May 11, 2004; ACCEPTED May 11, 2004)

A model for the human opioid receptor has been generated via sequence alignment, structure building using the crystal structure of bovine rhodopsin as a template, and refinement by molecular dynamics simulation. The model building suggested that, in addition to the previously postulated interaction between D128 and Y308, an internal salt bridge also exists between residues D128 and R192, both of which are conserved in all the opioid receptors. The model and salt bridge were then shown to be stable during a 20-nsec simulation in a lipid bilayer. It is therefore proposed that both of these interactions play a role in stabilizing the inactive state of the receptor. The model is also used in an effort to rationalize many of the mutational studies performed on opioid receptors, and to suggest a plausible explanation for the differences between known opioid agonists and antagonists.

Keywords: molecular dynamics; bovine rhodopsin; GPCR; agonist-antagonist binding; activation mechanism

Reprint requests to: Paul E. Smith, Department of Chemistry, 111 Willard Hall, Kansas State University, Manhattan, KS 66506-3701, USA; e-mail: pesmith{at}ksu.edu; fax: (785) 532-6666.

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.04720304.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Uribe, T. Zarinan, M. A. Perez-Solis, R. Gutierrez-Sagal, E. Jardon-Valadez, A. Pineiro, J. A. Dias, and A. Ulloa-Aguirre Functional and Structural Roles of Conserved Cysteine Residues in the Carboxyl-Terminal Domain of the Follicle-Stimulating Hormone Receptor in Human Embryonic Kidney 293 Cells Biol Reprod, May 1, 2008; 78(5): 869 - 882. [Abstract] [Full Text] [PDF]

				J. Henin, B. Maigret, M. Tarek, C. Escrieut, D. Fourmy, and C. Chipot Probing a Model of a GPCR/Ligand Complex in an Explicit Membrane Environment: The Human Cholecystokinin-1 Receptor Biophys. J., February 15, 2006; 90(4): 1232 - 1240. [Abstract] [Full Text] [PDF]