TICA-based state definitions may be preferable to RMSD-based definitions. We believe using TICA and slow motions to define states may be more robust than RMSD. In particular, we find that while there is some correspondence between our TICA-based state definitions and the RMSD to reference crystal structures (Figure ), definitions based on the dynamics of the system result in clearer boundaries between states. For example, we observe that trajectory frames close to the 4w59 crystal structure in TICA space generally have low RMSD to that structure (Figure ). However, some of these same frames also have low RMSD to the 4w57 crystal (Figure ), which would complicate any analysis which attempted to assign states based on RMSD cutoffs alone. Given the 4w57 and 4w59 structures are considered distinct in experiment, considering a structure to be similar to both states is confusing.