Superimposition of Screened Drugs within the Active Region on the EWS Protein. All the docked structures had been superimposed to verify the binding configurations of all five screened drugs inside the active area of the EWS protein. The binding pocket evaluation showed that all of the screened FDA-approved drugs were narrowed in the binding pocket and bound with similar residues with littledoi.org/10.1021/acsomega.2c00518 ACS Omega 2022, 7, 19243-ACS Omegahttp://pubs.acs.org/journal/acsodfArticleFigure 6. FDA-approved drugs and associations with ES.Table 7. Binding Affinities of Screened Docking Complexesdrugs chlorthalidone astemizole ketoconazole sulfinpyrazone pranlukast binding energy (kcal/mol) -4.88 -1.20 -0.66 -5.18 -11.84 drug efficacy 0.22 0.04 0.02 0.18 0.33 internal power (kcal/mol) 5.18 three.59 two.15 three.39 9.75 electrostatic (kcal/mol) 0.01 0.01 0.15 0.13 0.01 torsional power (kcal/mol) 0.3 2.39 1.49 1.79 two.diverse conformational poses inside the binding pocket of the EWS protein. The binding of all FDA-approved drugs in the same position justified the docking reliability and also the accuracy of predicted interactive final results (Figure 7). 3.six.two. Chlorthalidone Hydrogen Binding Evaluation. The chlorthalidone-EWS docked complicated is analyzed depending on the interaction pattern of binding pocket residues of EWS. The chlorthalidone binds with EWS possessing a good conformational position inside the active region encompassed by His399, Ile398, Leu374, Thr373, Val372, Pro409, and Leu402 residues, respectively. The oxygen atom in the thiol group in chlorthalidone formed hydrophobic interactions with His399 having a bond distance of 4.ten Additionally, an additional oxygen atom is present within the five-member ring on the drug forming a different hydrogen bond with Thr373 with a bond distance of two.66 In each chlorthalidone docking interactions both bonds offered superior steady behavior to the docking complex, and bond distances had been comparable to standard values (5 hydrophobic and 3 hydrogen bonds), respectively (Figure 8).3.six.three. Astemizole Hydrogen Binding Evaluation. In astemizole-EWS docking, astemizole binds within the target website of EWS with an acceptable conformational position through interaction with unique residues, His399, Ser416, Met397, Thr393, Gln395, Leu374, Ile400, and Ile398. The nitrogen atom on the amino group attached to a heterocyclic group formed a few hydrogen bonds with Ile398 and His399, with bond distances of two.Resiniferatoxin References 14 and three.Monensin Bacterial 06 respectively.PMID:26446225 Both astemizole interactions have superior comparable values with normal values (5 hydrophobic and three hydrogen bonds), respectively (Figure 9). 3.6.4. Ketoconazole Hydrogen Binding Analysis. In ketoconazole-EWS docking, the drug binds with site-specific residues with proper conformational behavior. Ketoconazole encompassed distinct Arg392, Asn390, Gln395, Leu374, Thr373, Ile402, Ile400, His399, Ile398, and Met397 residues. 4 hydrogen bonds have been observed among the ketoconazole-EWS docking complicated. The oxygen atom on the benzene ring formed tetrahydrogen bonds at Arg392 and Asn390 with bond distances of 2.04, two.81, 2.66, and 2.72 respectively.doi.org/10.1021/acsomega.2c00518 ACS Omega 2022, 7, 19243-ACS Omegahttp://pubs.acs.org/journal/acsodfArticleFigure 7. Superimposition of five docking complexes.Figure 9. Astemizole-EWS docking complicated. The EWS structure is represented in light pink color, whereas the binding pocket of the EWS protein is highlighted in gray color inside the surface format. The res.