Protein activation and deactivation is central to a variety of biological mechanisms, including cellular signaling and transport. Unimolecular fluorescent resonance energy transfer (FRET) probes are a class of fusion protein sensors that allow biologists to visualize using an optical microscope whether specific proteins are activated due to the presence nearby of small drug-like signaling molecules, ligands or analytes. Often such probes comprise a donor fluorescent protein attached to a ligand binding domain, a sensor or reporter domain attached to the acceptor fluorescent protein, with these ligand binding and sensor domains connected by a protein linker. Various choices of linker type are possible ranging from highly flexible proteins to hinge-like proteins. It is also possible to select donor and acceptor pairs according to their corresponding F��ster radius, or even to mutate binding and sensor domains so as to change their binding energy in the activated or inactivated states. The focus of the present work is the exploration through simulation of the impact of such choices on sensor performance.