Our final elaboration dataset is a set of fragment merging decisions for a fragment screen of Cyclophilin D by Gradler et al. . Here we simulate a subset of the ligands investigated in the original study, covering a total of 5 merging decisions (SI Fig. , SI Table ). We again find good correlation between the calculated and experimental free energies, with a Pearson r of 0.91 ± 0.10 and a Kendall 𝜏 0.69 ± 0.19 albeit with a relatively large RMSE of 2.57 ± 0.33 kcal/mol. For the most part (with ligand 2 being an exception) this seems to represent a systematic shift in the free energy by approximately 2.5 kcal/mol (Fig. ).