Fig. 6: The updated pheromone model responds as expected to pheromone. | npj Systems Biology and Applications

Fig. 6: The updated pheromone model responds as expected to pheromone.

From: A scalable method for parameter-free simulation and validation of mechanistic cellular signal transduction network models

Fig. 6

We generated a bBM form the updated pheromone model and (I) simulated it in the absence of pheromone (unbound pheromone set to false) until the first steady state, where (II) free pheromone was set to true, representing pheromone stimulation, and the simulation repeated until next steady state was reached, before (III) pheromone was removed (by setting both free and bound pheromone to false) and the model simulated to the next steady state. The pathway turns on and off as expected, and finds a natural off state in the first simulation despite two activation pulses that go through the pathway. These are due to proteins that activate the pathway in their neutral states: the upstream Ste4, as discussed in the text, and the Ste12 transcription factor—which, according to the model, is active when not bound to Dig1 and Dig2. However, both pulses are transient and the steady state is robust against these transient dynamics. Panel (a) displays the input and output trajectories and panel (b) all the 248 state and reaction trajectories with the 149 unregulated targets condensed to three lines. Grey lines in (b) indicate the input/output states as displayed in (a).

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