Model simulations of time-course and dose–response curves for motifs 1–3. (a,b) Comparative temporal dynamics of the active output at increasing E3 ligase abundance for motif 1 and 3, respectively. Parameter values used: high [E3] = 1000 nM, medium [E3] = 100 nM, low [E3] = 10 nM, the remaining parameters are given in the SI. (c) Steady-state dependence of the active output on the Kinase abundance compared for motifs 1 and 2. (d) Steady-state dependence of the active output on the E3 ligase abundance compared for three motifs 1–3.