In this study we used datasets that have previously been used for relative binding free energy calculations. We observed how the absolute calculations could return good correlations, with the apo state affecting the offset seen in terms of the larger AUE. In other words, the difference in apo state conformation and energy had a consistent effect for the binding free en-ergy of the ligands for each target. It remains to be seen if that will hold true as the diversity of the ligands increases, even if they are binding in the same site. We anticipate that future studies on an even larger scale will be required to examine these effects.