Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site
Joint Authors
Cordomi, Arnau
Martinez-Archundia, Marlet
Perez, Juan J.
Garriga, Pere
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-02-27
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
The present study reports the results of a combined computational and site mutagenesis study designed to provide new insights into the orthosteric binding site of the human M3 muscarinic acetylcholine receptor.
For this purpose a three-dimensional structure of the receptor at atomic resolution was built by homology modeling, using the crystallographic structure of bovine rhodopsin as a template.
Then, the antagonist N-methylscopolamine was docked in the model and subsequently embedded in a lipid bilayer for its refinement using molecular dynamics simulations.
Two different lipid bilayer compositions were studied: one component palmitoyl-oleyl phosphatidylcholine (POPC) and two-component palmitoyl-oleyl phosphatidylcholine/palmitoyl-oleyl phosphatidylserine (POPC-POPS).
Analysis of the results suggested that residues F222 and T235 may contribute to the ligand-receptor recognition.
Accordingly, alanine mutants at positions 222 and 235 were constructed, expressed, and their binding properties determined.
The results confirmed the role of these residues in modulating the binding affinity of the ligand.
American Psychological Association (APA)
Martinez-Archundia, Marlet& Cordomi, Arnau& Garriga, Pere& Perez, Juan J.. 2012. Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site. BioMed Research International،Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-991897
Modern Language Association (MLA)
Martinez-Archundia, Marlet…[et al.]. Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site. BioMed Research International No. 2012 (2012), pp.1-12.
https://search.emarefa.net/detail/BIM-991897
American Medical Association (AMA)
Martinez-Archundia, Marlet& Cordomi, Arnau& Garriga, Pere& Perez, Juan J.. Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site. BioMed Research International. 2012. Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-991897
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-991897