Figure 7:

The distribution of RMSDs to a ligand-bound reference structure as the concentration of the ligand is varied. The $\mathrm{Y}$ axis is ligand concentration, and the $\mathrm{X}$ axis is the pocket-aligned Ligand RMSD to holo crystal structure, histogrammed as before (Fig. 4). Each row in each heatmap is from the same raw data being histogrammed with different weights, computed by plugging the Y-value matching that row into Eq. 38. The orange line on each replica plot shows the ${\mathrm{K}}_{\mathrm{D}}$ as calculated for that replica using 33 , and is shown for reference. The top row in each heatmap is holo-like, because it is at high ligand concentration, and the bottom row is apo-like because it is at low ligand concentration. Being able to titrate observables measurable from conformations in this way could provide exciting opportunities to understand ligand efficacy in systems with allosteric behavior. marked by an orange line.