Fig. 1.
The basic and cubic allosteric ternary complex mechanisms. A, the ATCM, a concise framework for modeling the interaction of two ligands (e.g., an orthosteric agonist A and an allosteric modulator, B) on a receptor, in terms of their respective equilibrium dissociation constants (KA and KB), and a cooperativity factor, α, that denotes the magnitude and direction of the allosteric effect on ligand binding affinity. Stimulus is assumed to be imparted to the cell by the orthosteric agonist binding receptor (AR) and the modulator-orthosteric agonist binding species (ARB), and an additional proportionality factor, β, may be added to account for modulator-induced alterations in efficacy. B, the allosteric CTC model. This model allows the active state to interact with G protein and the inactive R* state. This model is formally identical with the allosteric two-state model of Hall (2000), which describes the interaction of an allosteric modulator and orthosteric ligand on a receptor that can adopt active and inactive conformations. The terms β, γ, and δ (for the CTC model) are ligand-related and describe the change in the receptor affinity, for the G protein, imparted by the ligand.