Based on SHAP feature importances, the most important features on the 5 cross-validation sets are the PM6/COSMO interaction energy (Eint), many of the PLEC UMAP projections, and the following 2D ligand descriptors: bondType_SINGLE, bondType _AROMATIC, MW, ring_flexibility, AMW, deepFl_logP, function_group_count. Remarkably, the same features score first in a retrospective SHAP calculation on the external test sets but in a different order. Features that are not UMAP projections of PLEC fingerprint are colored red. B) The SHAP feature importances as calculated when all 16 datasets but GR were used for training during the LORO cross-validation. C) The worst scored compounds (ligands start with "bdb" and decoys with "zinc") by SQM-ML when all 16 datasets but GR were used for training.