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Conformation Guides Molecular Efficacy in Docking Screens of Activated β-2 Adrenergic G Protein Coupled Receptor
- Source :
- ACS Chemical Biology; May 2013, Vol. 8 Issue: 5 p1018-1026, 9p
- Publication Year :
- 2013
-
Abstract
- A prospective, large library virtual screen against an activated β2-adrenergic receptor (β2AR) structure returned potent agonists to the exclusion of inverse-agonists, providing the first complement to the previous virtual screening campaigns against inverse-agonist-bound G protein coupled receptor (GPCR) structures, which predicted only inverse-agonists. In addition, two hits recapitulated the signaling profile of the co-crystal ligand with respect to the G protein and arrestin mediated signaling. This functional fidelity has important implications in drug design, as the ability to predict ligands with predefined signaling properties is highly desirable. However, the agonist-bound state provides an uncertain template for modeling the activated conformation of other GPCRs, as a dopamine D2 receptor (DRD2) activated model templated on the activated β2AR structure returned few hits of only marginal potency.
Details
- Language :
- English
- ISSN :
- 15548929 and 15548937
- Volume :
- 8
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- ACS Chemical Biology
- Publication Type :
- Periodical
- Accession number :
- ejs29944463
- Full Text :
- https://doi.org/10.1021/cb400103f