Our data supports the assumption of a direct correlation between molecular similarity and PLIF similarity. For DiffDock-L poses of molecules that are structurally distinct from any measured ligand structures (with Tanimoto coefficients not exceeding 0.30), the median PLIF similarity was 0.55 (Figure ; refer to Figure for results on the individual targets). In contrast, for structurally related pairs of molecules (with 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 aligned 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 0.57). 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 DiffDock-L and Vina for 43 DUDE-Z targets.