Another caveat to take into account when correlating docking pose quality with alchemical calculation accuracy is that the reported absolute ΔG values are only reconstructions from the relative ΔΔG estimates . This means that accurate/inaccurate predictions may not necessarily be caused by the inappropriate pose of a ligand itself, but also of its neighbors to which it was mapped in the ligand perturbation map. All in all, for a systematic study of the starting pose effects on the affinity prediction accuracy one would require a particular system setup with well controlled structural changes or rely on absolute binding affinity calculations .