(5 mappings), TYK2 dataset 2% (5 mappings) and HIF2A 1% (12 mappings). A visual inspection of the exceptional cases showed a few reasons for the outliers. In a substantial number of cases, the SIS-based approaches 're-aligned' the ligands to maximize the number of mapped atoms (see Figure and SI-Figure ). This was quantified by counting how often more than 3 atoms got displaced with a distance larger than 1.2 Å in a mapping.