Finally, the free energies of each transformation were estimated using MBAR 97 via pymbar. The whole procedure was repeated three times with different random seeds, to assess the sampling uncertainty of the approach. Cinnabar 99 was used for the network-wide free energy analysis over a full set of ligands. The bootstrap error estimate for the statistics (such as the RMSE, MUE, ρ spear , and τ kendal ) was estimated over all replicates with SciPy. Test Systems