Slowest motion of congeneric ligand systems corresponds to opening of the F-helix. We combine simulation data from all three native systems together in order to ensure the slowest motion of our system corresponds to the opening of the F-helix and/or any important differences between these native systems. For clarity, these three native systems are benzene bound to T4 L99A started from the 4w52 structure (4w52-benzene), butylbenzene bound to T4 L99A started from the 4w57 structure (4w57-butylbenzene) and hexylbenzene bound to T4 L99A started from the 4w59 structure (4w59-hexylbenzene) (see Methods for more explanation on terminology). Specifically, we expect these native systems to occupy three distinct states with no or few transitions between them. Thus, a concatenated trajec-tory of these native systems would show distinct transitions between states at the end of each of the individual component trajectories, turning these state transitions into easily recognizable "slow motions". This allows us to resolve a set of time-lagged independent components (tICs) that can be used to categorize the frames of each trajectory into discrete states.