What is biased efficacy? Defining the relationship between intrinsic efficacy and free energy coupling

Highlights • GPCR signalling involves interactions with multiple transduction proteins. • Differences in the agonist-induced cooperative effect that stabilizes distinct receptor–transducer complexes generate biased agonism. • This cooperative effect is mathematically related to the intrinsic efficac...

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Bibliographic Details
Published in:Trends in pharmacological sciences (Regular ed.) 2014-12, Vol.35 (12), p.639-647
Main Authors: Onaran, H. Ongun, Rajagopal, Sudarshan, Costa, Tommaso
Format: Article
Language:English
Subjects:
Advanced Basic Science
GPCR
Kinetics
Receptors, G-Protein-Coupled - agonists
Receptors, G-Protein-Coupled - chemistry
Receptors, G-Protein-Coupled - metabolism
Thermodynamics
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Summary:Highlights • GPCR signalling involves interactions with multiple transduction proteins. • Differences in the agonist-induced cooperative effect that stabilizes distinct receptor–transducer complexes generate biased agonism. • This cooperative effect is mathematically related to the intrinsic efficacy of classical receptor theory. • This relationship provides a rational approach to quantifying biased efficacy.
ISSN:0165-6147
1873-3735
DOI:10.1016/j.tips.2014.09.010