  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\"oster 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.
