The thus computed relative free energies were added to the experimentally measured free energy of the reference ligand to generate the absolute binding free energies used for training. This approach yields accurate predictions of free energies, which we benchmarked on a subset of ligands from the experimental library from Part I that share the same scaffold as the prospective library (55 molecules). The absolute unsigned error compared to the experimental measurement was 0.8 ± 0.1 kcal/mol (Fig. ). The benchmarked compounds together with the reference ligand (55 molecules total) also appear in the currently investigated prospective library and, so, are used for validation of model predictions (Fig. ).