Table 1 Experimentally validated H1R hits based on the IFP and PLANTS approach.

From: Function-specific virtual screening for GPCR ligands using a combined scoring method

  1. aThe letters C, I and P, refer to the distinct compound selections from each the Combined, IFP and PLANTS scoring approach, respectively. Combinations like C + I indicate that the compound was present in both the selection of the Combined and the IFP scoring approach but not the PLANTS approach. Further details are shown in Fig. 3. bpKi values are calculated from at least three independent measurements as the mean ± SEM. Measured by displacement of [3H]-mepyramine binding using membranes of HEK293T cells transiently expressing the human H1R. cIFP Tanimoto similarity to the pose of doxepin in the H1R crystal structure. Optimized IFP score cut-off ≥0.75. IFP ranking is given between brackets. dScore and rank according to PLANTS scoring function19. Optimized PLANTS score cut-off ≤−90. PLANTS ranking is given between brackets. eROCS shape-based 3D similarity to doxepin based on Comboscore69. ROCS ranking is given between brackets. fECFP-4 2D Tanimoto similarity to doxepin. A similarity higher than 0.40 is considered as significative21. ECFP-4 ranking is given between brackets. gECFP-4 circular fingerprint Tanimoto similarity to closest known H1R active in ChEMBLdb. A similarity higher than 0.40 is considered as significative21. hThe closest known H1R active in the ChEMBLdb as determined by the ECFP-4 similarity.
    Figure 3
    figure3

    Hit rate analysis for each of the scoring approaches.

    Bar-plots summarizing the hit-rates and the affinity/potency of the experimentally validated hits for both (a) the H1R and (b) the β2R virtual screening. (c) Analysis of the hit-rates for each of the scoring methods and all possible combinations thereof (as highlighted in panel (d)) for both H1R and β2R. Hit rates for each set (panel (d)) are reported as the number of hits and the total number of tested compounds followed by the hit rate percentage. (d) Venn diagram highlighting the different scoring combinations used for the analysis of H1R and β2R hit-rates in panel (c).