Figure 5.

Schematic diagram of operational modeling parameters. (A) Schematic of an mGlu dimeric receptor. Glutamate or orthosteric agonists (red circle) bind in the large extracellular binding domain of the mGlus, and modulators (blue stars) bind in the transmembrane domains. K_A represents orthosteric agonist affinity, while K_B is allosteric modulator affinity. The results shown here demonstrate interactions between the allosteric and orthosteric sites in terms of affinity modulation. Affinity modulation is governed by the cooperativity factor α, and efficacy modulation is governed by β. The parameters τ_A and τ_B represent the ability of orthosteric agonist and allosteric ligands, respectively, to directly activate the receptor. (B) Interaction of allosteric parameters and effects on response shown using the allosteric ternary complex model. Adapted from ref (42).