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Decoupling between activation time and steady-state level in input-output responses
Fig 5
Decoupling from an equilibrium of initial states.
(A) Schematic of the 
definition of activation time. This definition assumes that, before the ligand is introduced, the system has reached a steady state over the unbound states. That is, at the moment immediately prior to the introduction of ligand (t = 0 and x = 0), the system may occupy any of the unbound states (red vertices), each according to its steady-state probability. (B) Distributions of the coupling score, f, obtained from optimization with various rate scale constraints (RSC). Only the parameter sets for which f < 1 are shown, and their number for each RSC value is given underneath the corresponding set of points. (C) Input-output responses corresponding to the parameter sets obtained from optimization with RSC = 0.005, for which f < 1 and 
increases with x. (D) Values of 
and 
in the parameter sets corresponding to the responses in C (RSC = 0.005). (E) Parameter values corresponding to the responses in C (RSC = 0.005). The green line represents the best parameter set. Each parameter is plotted in units of 
, except for kon, which is in units of 
. (F) Heatmap of the coupling score, f, with respect to 
and 
, with the other parameters set to the most optimal parameter set (green curve in E), along with select choices of 
and 
(crosses) whose corresponding input-output curves are shown in G. (G) Input-output curves corresponding to the parameter sets indicated in F. (H) Values of 
and 
in the best parameter set for each choice of RSC.
doi: https://doi.org/10.1371/journal.pcbi.1014288.g005