*2.3.2 Concept pros*

Protein-fragment complementation is usually performed using living cells allowing proteins to be maintained in relatively native conditions. Reporter activity often have an amplification step that allows for the sensitive detection of even weak interactions [26]. While protein-fragment complementation technically reads out proximity, reasonable linker lengths can select for small distances. The interaction has to persist long enough for the activity to be reconstituted, reducing false positives rates when compared to some other proximity-based techniques.

## *2.3.3 Concept cons*

Protein-fragment complementation mandates the tagging of proteins with nonnative sequences for the reporter readout. These tags can be substantial in size and affect the behavior of the proteins being tagged. Since the reporter activity depends only on the reporter portion being in close proximity, this approach does not guarantee a direct interaction. Most systems only test binary interactions by design since only the tagged proteins are being assayed.
