Interestingly cis-SIM1 tracked nearly identically with MT1 in both BRD2 and BRD4 traces (Fig. ) indicating that cooperative engagement of VHL improves residence time of SIM1 vs cis-SIM1. Further experiments which were performed with (R,S)-SIM1, MZ1, and cis-MZ1 revealed enhanced residence times of MZ1 and (R,S)-SIM1, though neither as significant as for SIM1 (Extended Data Fig. ). The increase observed from cis-MZ1 to MZ1 (Extended Data Fig. ) again supports that cooperative ternary complexes can increase residence time, yet not to as great of extent as SIM1 as it is lacking the added avidity. Together, the results indicate that SIM1 favorability for BRD2 is facilitated by intramolecular binding that results in both a structural change as well as extended ternary complex half-life.