Example of drug synergism in FBA. For the toy network depicted in(A) the aim is to stop the objective reaction v10 (inred) by choosing a combination of drugs (the three valves “⋈”)while blocking the minimum number of reactions other than v10.In the drawing, blue arrows indicate active fluxes while gray arrows refer tostopped reactions; the valve is red if the drug is used, gray otherwise. Panel(B) shows how the use of a single drug (v4 orv7) does not stop the objective reaction, while the drug atv2 blocks the objective reaction v10but it also blocks all fluxes of the network (panel (C)). Therefore, theoptimal drug combination blocking the objective function v10with minimal side effect is given by the synergism of the two drugs acting atv4 and v7 (panel (D)). Thecomparison of panels (B) and (D) shows how a synergism is a behaviorwhich cannot be simply inferred by the superposition of the effects of the singledrugs, but that structurally depends from the topology of the network.