Briefly described, embodiments of this disclosure include bioluminescence resonance energy transfer (BRET) systems, methods of detecting a protein-protein interaction, noninvasive methods for detecting the interaction of a first protein with a second protein within a living animal, methods to determine the efficacy of a test compound administered to modulate the interaction of a first protein with a second protein in a living animal, BRET vectors, kits relating to each of the above, transgenic cell or progeny thereof and/or animals relating to each of the above, and the like.