Pharmacological affinity fingerprints derived from bioactivity data for the identification of designer drugs

Facing the continuous emergence of new psychoactive substances (NPS) and their threat to public health, more effective methods for NPS prediction and identification are critical. In this study, the pharmacological affinity fingerprints (Ph-fp) of NPS compounds were predicted by Random Forest classification models using bioactivity data from the ChEMBL database. The binary Ph-fp is the vector consisting of a compound’s activity against a list of molecular targets reported to be responsible for the pharmacological effects of NPS. Their performance in similarity searching and unsupervised clustering was assessed and compared to 2D structure fingerprints Morgan and MACCS (1024-bits ECFP4 and 166-bits SMARTS-based MACCS implementation of RDKit). The performance in retrieving compounds according to their pharmacological categorizations is influenced by the predicted active assay counts in Ph-fp and the choice of similarity metric. Overall, the comparative unsupervised clustering analysis suggests the use of a classification model with Morgan fingerprints as input for the construction of Ph-fp. This combination gives satisfactory clustering performance based on external and internal clustering validation indices. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13321-022-00607-6.