In silico prediction of ERK activation patterns under weak, intermediate, or strong stimulations. ERK activation in cells with wild-type SOS, without SOS, or with allosteric mutant W729E SOS expression is projected at increasing time points. Each plot is a histogram of 8,000 realizations from stochastic simulations. (A to C) In the simulations, there is no negative feedback loop from ERK to SOS or positive feedback loop in the RAF-MEK-ERK module. (D to F) The negative feedback loop from ERK to SOS is added. (G to I) The simulations include both the negative feedback loop from ERK to SOS and the modest positive feedback loop in the RAF-MEK-ERK module.