In Figure , we define our macrostates or metastable binding modes by assigning each microstate to a given K number of macrostates via PCCA. To determine the appropriate number of K macrostates to use, we evaluate the clustering using silhouette scoring Figure : Left: Time-lagged independent component analysis (TICA) plot for binding modes of 8NY located in the right sub-cavity using the first two TICA components from our BLUES simulations. Discrete microstates (i.e. simulation frames are denoted by Xs. Each microstate has been assigned to a macrostate by PCCA which define our metastable binding modes sampled during our simulation. We find 3 states (red, green ,blue) or binding modes sampled from simulations of 8NY in the right sub-cavity. Right: Shows the sampling density from our BLUES simulations for the 3 macrostates defined by PCCA, where tighter clusters are suggestive of higher stability for that particular macrostate.