The NPFC analyses were performed on an in-house cluster (4 nodes, 96 cores), using Python 3.9 and the NPFC tool in the latest version, available at . All further downstream processing and cheminformatics analyses were performed locally, using Python 3.11 and the RDKit, v2023.03.1. The normalized Spatial Score was calculated from the standardized SMILES using the code accompanying lit. Note: since v2023.09.1, SPS and nSPS are implemented directly in the RDKit.