In native mass spectrometry (nMS) for structural biology, insource collisional activation is often used to clean up biomolecules and complexes that are adducted by salt and water molecules. This strategy can result in 'cleaner' biomolecules and narrower peaks that increase spectral resolution. These two outcomes result in deconvolved masses that are accurate, and easier to obtain than when the complex is 'adducted,' leading to broad peaks. In-source collisional activation (isCA) can also be used as a pseudo-MS n step to dissociate the precursor macromolecular complex, or dislodge native ligands, for targeted experiments downstream from the source. However, it is also known that isCA can cause native-like biomolecular complexes to restructure such that downstream activation steps and analyses do not reflect the native-like structure. Hence, it is critically important to balance the need for 'cleaner' mass spectra with the need to produce ionized biological macromolecular complexes that produce data reflecting the native-like structure and chemistry. However, it can be difficult to ascertain what degree of isCA is appropriate, while also resisting the natural urge to obtain spectra that look 'nice', i.e., spectra with narrow, resolved peaks. This paper seeks to illustrate why care must be taken with isCA when pursuing nMS, by using surface-induced dissociation and electron capture dissociation as tools to develop appropriate "native" instrument tuning. In particular, this paper assesses native-like tuning for a cyclic IMS QTOF instrument with a commercial implementation of SID installed after the selection quadrupole.