Protein-protein interactions orchestrate much of biological function. High-affinity interactions enable protein circuits to respond to low concentrations of stimuli and to act potently on targets; fast exchange enables them to respond quickly to changes in stimuli. These two properties cannot usually be achieved simultaneously in binary interactions because they depend on the interaction off-rate in opposite ways: high affinity usually requires slow dissociation (low off-rate), whereas rapid exchange requires fast dissociation (high off-rate) (Supplementary Fig. 1).