Figure 6. The extended ATSM with two allosteric ligands.

(A) The model has ten species related by four equilibrium cycles with seven parameters. The first equilibrium cycle (orange) specified by the , , and is exactly the same as in the simplest ATSM (Figure 2A), giving the equilibrium constant between the two states, the binding affinity of ligand bound to inactive , and the allosteric intrinsic efficacy of ligand . The second equilibrium cycle (pale green) describes the second ligand binding similar to the first ligand binding, assigning and respectively as the binding affinity and the allosteric intrinsic efficacy of ligand . In the third equilibrium cycle (cyan), the sixth parameter administers the binding cooperativity between ligand and upon the formation of the ternary complex . Similarly, the seventh parameter governs the activation cooperativity between ligand and through the formation of in the fourth equilibrium cycle (red). (B) The complete equilibrium cycles of the extended ATSM. The four essential equilibrium cycles of the extended ATSM in (A) are combined into a cubic shape of a complete cycle. To guide the visualization, the two corners of the complete cycle are highlighted by colored equilibrium arrows for species and and colored parameters for referencing back to the individual essential equilibrium cycle. (C) The structural view of allostery with two allosteric site and two (independent) functional sites. The drawing is based on two assumptions. First, the populations of the two functional sites are regulated independently by two distinct allosteric sites. Second, the two functional conformations coexist. The allosteric coupling set (, , and ) for functional site 1 and a duplicated set of independent allosteric efficacies (, , and ) for functional site 2 are similar to the description in Figure 6B. These two sets of coupling are linked by a shared binding cooperativity γ, coupling the two allosteric sites.