Figure 1.

Schematic diagram showing the relevance of the Black–Leff operational model to quantification of agonist bias. The premise is based on the fact that the receptor conformation stabilized by the agonist will have a unique interaction with all signaling proteins that directly interact with it, thereby setting up the allosteric system(s) of modulator (agonist)/conduit (receptor)/guest (signaling protein). Under these circumstances, the affinity and the efficacy (the “quality” of the conformation) will be determined by the signaling protein, and this will be unique for each pathway. The magnitude of log(τ/K_A) will be characteristic of both the affinity and efficacy of the agonist for a particular pathway.