For data preparation and modeling, the python package QSPRpred was used. For all models, the same datasets were used. Bioactivity was expressed in pChEMBL values, i.e., the negative logarithmic of either the scaled half-maximal response concentration, potency or affinity values. For compoundprotein pairs with multiple measurements, either the median pChEMBL value of all measurements was used (control), or the median pChEMBL value of the assays from the same category (multi-task) or with the same description (assay descriptor). Molecules were standardized and then described using extended-connectivity fingerprints with a radius of 3 bonds and were folded to 2048 bits (ECFP6). The protein sequences for each protein family were aligned separately via multiple sequence alignment using Clustal Omega (final alignment is available here: