Annihilation of limit-cycle oscillations by identification of critical perturbing stimuli via mixed-integer optimal control.

We present a novel model-based mixed-integer optimal control method to automatically identify the strength and timing of critical external stimuli leading to the transient annihilation of limit-cycle oscillators. Biochemical oscillators of this type play a central role in regulating cellular rhythms. Their specific manipulation is a promising perspective to control biological functions by drugs and tailored treatment strategies. We demonstrate our new optimal control approach in an application to a biochemical model for oscillatory calcium signal transduction.