Fig. 4

Results of differential docking of morphine- and fentanyl-related ligands. A Distribution of docking scores, i.e., binding free energies \(\Delta F_P(\text {pH}= 7.4)\) and \(\Delta F_P(\text {pH}=5.0)\), for ligand library A at neutral and acidic pH. Paired t-test, two-tailed. B Docking scores of morphine- and fentanyl-related molecules to the MOR at neutral (x-axis) plotted against docking scores to the MOR at acidic pH (y-axis). Reference compounds [morphine (red), fentanyl (magenta), NFEPP (green), \(\beta\)-fluorofentanyls (neon green), \(\beta\)-fluoromorphines (orange)] and pH-specific hit compound [CHEMBL3139481 (blue)] are highlighted. Data points indicate mean docking scores, horizontal lines indicate standard error of the mean (SEM) of neutral pH scores, and vertical lines SEM of acidic pH scores. C Comparison of the MOR docking scores of fentanyl, NFEPP, morphine and CHEMBL3139481 obtained under neutral and acidic pH conditions. Individual data points show scores of replicate dockings, horizontal bars indicate mean values, and error bars indicate standard deviations (SD). Mean docking scores were analyzed by two-way ANOVA with Šídák’s multiple comparisons test