Our data confirms the assumption of a direct correlation between molecular similarity and PLIF similarity: For Vina poses of molecules structurally distinct from any measured ligand structures (Tanimoto coefficients not exceeding 0.30), the median PLIF similarity was 0.57 (Figure ; see Figure for results on the individual targets). In contrast, for structurally related pairs of molecules (Tanimoto coefficients greater than 0.75), the median PLIF similarity was 0.67, which is significantly higher (Welch's t-test 𝘱-value < 10 -4 ). The results for DiffDock-L were consistent with the observations for Vina. With a median of 0.67, the PLIF similarity was significantly higher (Welch's t-test 𝘱-value < 10 -4 ) for the bin of structurally related pairs of compounds than for the bin of structurally distinct compounds (median 0.55). Figure . PLIF similarities between pairs of (A) structurally distinct measured and predicted protein-ligand complexes and (B) structurally related measured and predicted protein-ligand complexes sampled with Vina and DiffDock-L for 43 DUDE-Z targets.