Model for FRET sensors of allosteric switchable modulator proteins for the determination of allosteric parameters

FRET-sensors are a well-established method to investigate protein-protein interactions. To determine how FRET-sensor can be employed for the study of switchable allosteric modulator proteins (SAMPs) I extend a previously established model for enzymatic SAMPs to include a FRET-sensor system. Using this model, I determine the prerequisites for using FRET to investigate modulator-regulator interaction. The model shows, that under saturating stimulus conditions only a trimolecular complex contributes to the measured FRET value. How the signal is relayed by the modulator can be investigated by comparing FRET values of unstimulated and signal-saturated sensor systems. Finally, to determine the allosteric mode of signal transduction the natural logarithm of the ratio of stimulated and unstimulated FRET efficiencies is a useful metric.