Remarkably, these structures also aid in deducing why the most potent state of AzTG-2 and AzTG-4 is the transconfiguration, while for AzTG-6 it is the cis-configuration. The cavity where the AzTG-4 photoswitch (and almost certainly the AzTG-2 photoswitch) resides is relatively accessible, but small in volume. Consequently, the size of the cavity itself may result in one photoisomer being preferred over the other. Thus, for trans-AzTG-2 and trans-AzTG-4, the in-line and in-plane geometry of the azobenzene phenyls may provide the arrangement which minimises conflict with surrounding residues. In contrast, the cavity where the AzTG-6 photoswitch resides is relatively large, but lies further away from the surface. Therefore, accessibility is more likely to affect photoisomer preference. In this case, we hypothesize that the more compact and rigid photoswitch of cis-AzTG-6 is able to more easily insert between the M3 and M5 helices and bind within the TM domain.