Fig. 6: The relationship between the VLS performance and the ‘correctness’ (geometric accuracy) of experimental structures and computationally predicted models from GPCR Dock assessments 2010 and 2021.
From: AI meets physics in computational structure-based drug discovery for GPCRs
a, c, e Scatter plots of retrospective VLS ROC AUC values (x-axis) against ‘correctness’ (y-axis) for 23 selected GPCR Dock 2010 models and two chains of the X-ray structure of the dopamine D3 receptor-eticlopride complex (a), as well as for 10 selected GPCR Dock 2021 models and six cryo-EM structures of the GPR139-JNJ-63533054 complex (c, e). The ROC AUC values in (c) and (e) were obtained using the same set of active compounds but different sets of decoys/inactives: the DUDe-generated set of compounds that are highly chemically dissimilar from actives (Tanimoto distance (TD) > 0.5, c) vs a comparable size set of ChEMBL compounds that are more chemically similar (0.1 < TD < 0.5) to the actives but have no known activity at GPR139 (e). b, d, f Retrospective VLS ROC curves for selected experimental structures (brighter color), more accurate models (lighter color), and less accurate models (black) from (a, c, e). Figure was created using using R 4.4.1159, and ggplot2 3.5.0160.
