In the SARS-MP-76 cross-docking set, the complexes generally show a good resolution and low DPI, but the ligands display relatively numerous crystal contacts and have a low median EDIAm value (Figure ). Many ligands stem from a fragment-screening study, therefore the median number of rotatable dihedrals is very low (Figure ). The cavity of the SARS-CoV-2 main protease is notably open and exposed to solvent (Figure ), which leads to a median ligand buriedness of only 0.75 (Figure ). The cavity contains four subcavities 83 (Figure ), which can be problematic for docking fragments and small ligands, as they can easily bind to different cavities owing to their low specificity. In summary, the SARS-MP-76 set is the most challenging set for docking.