Scalable Rule-Based Modelling of Allosteric Proteins and Biochemical Networks
Figure 4
Cooperative binding of competitive ligands to the concerted and sequential models.
The allosteric equilibrium of an unligated protein favours a state T (or t). Ligand L0 binds preferentially to state R (or r) and so binds cooperatively to the protein. The Hill coefficient of the dose-response function for L0 (the number of L0 bound to the protein versus the concentration of L0) was measured in the presence of increasing concentrations of three competing ligands: L1 favours the R state; L2 is neutral; L3 favours the T state. Concentrations of competing ligands are normalized to the EC50 of their own occupancy function. For the concerted model KRT = 103; for the sequential (tetrahedral) model Krt = 0.1 and ΓS = 10. Ligand affinities were set to KRLi = KrLi = (Γi)−1/2 and KTLi = KtLi = (Γi)1/2 with Γ0 = Γ1 = 0.01 (prefers R or r), Γ2 = 1 and Γ3 = 100 (prefers T or t).