This paper defines conditions to be used to keep protein complexes "native-like" in a cyclic IMS (q-IM-TOF) modified to include SID and ExD capabilities. Using Ubq 6+, with a goal of achieving a compact conformation that is considered in the literature to be native-like, we tuned the pre-IM voltage gradients to be as non-activating as possible. During this process we identified the post-Trap ion guide bias and the helium cell as the most activating regions, while adjusting the StepWave voltages resulted in minimal CCS changes. While such tuning was ideal to maintain Ubq's native-like structure, the shallow voltage gradients resulted in poor SID product transmission for the larger standard protein complex CRP. We then systematically increased the post-Trap ion guide bias and the helium cell entrance, exit, and bias voltages to obtain good SID product ion transmission for this larger, more structurally stable protein complex, noting that the new conditions did not cause non-native fragmentation behavior. Taking lessons from Ubq, we maintained the instrument's source, including the StepWave and cone voltage at low values as an added measure to preserve native-like structure for a range of standard protein complexes. We then systematically demonstrated that using the cone voltage setting for isCA to remove non-covalent adducts from protein complexes can result in both internal heating resulting in secondary fragmentation and, at higher energies, quaternary structure rearrangement. These effects were illustrated by using SID product ion distributions, CIx mobiligrams, and ECD. Secondary fragmentation, resulting from the additive nature of isCA and SID, altered fragmentation patterns and highlighted the importance of minimizing ion activation prior to the desired tandem MS steps even at isCA energies where drift time shift is not yet apparent. The approach reported here, that uses SID, CIx, and/or ECD of standard protein complexes, will be used to characterize native-like behavior in other instrument platforms in the future, to establish a standard "native" tuning protocol for new instrument acquisitions, released instrument modifications, or new practitioners of native MS.