e are 5.11, -1.33 and 0.84, respectively. Table S6 shows a summary of your HDAC11 MedChemExpress scoring functions of each of the interaction forces in between the molecular ligands in the studied compounds and also the proteins. The docking benefits show that all newly made molecules (Total-score: five.65-6.01) possess a larger total score function than compound 33 (Total score: five.11), indicating that the newly developed molecules possess a great stability around the active web site with the 7JYC protein. Compound 1-02 shows superior docking score. Compounds two,three,7,8,25,26,27,29 have low predicted activity, along with the total scoring function is fairly low, indicating that theoretically these compounds have a low antiviral potential. Precisely the same docking protocol is used to hyperlink each of the designed molecules to the active web page of your target protein. The orientation within the docking pocket and also the hydrogen bonds formed with surrounding amino acids are shown in Fig. ten and Fig. S5. The interaction in between compound 1-01 as well as the active binding web page of 7JYC is shown in Fig. 10(a). Compound 1-01 types hydrogen bond donor interaction with GLN192 (N-HN:two.545 ), ALA194 (O-H-N:two.034 ) and VAL186 (O-H-N:2.034 ); the hydrophobic channel consists of Met165, Pro168, Ala191, and Thr190. Total-score, Crash score and Polar score are five.66, -1.38 and 1.30, respectively. When compound 1-02 interacts together with the active area of the target protein (Fig. 10(b)), it really is observed that it types a hydrogen bond with GLU166 (O-H-O:1.825; it features a hydrophobic effect with Met165,J.-B. TONG, X. ZHANG, D. LUO et al.Chinese Journal of Analytical Chemistry 49 (2021) 63Fig. 11. Residual plots of Topomer CoMFA model (a) and HQSAR model (b).His41, Met49, Leu167, and Pro168. Total-score, Crash score and Polar score are 6.01, -2.45 and 1.09, respectively. In Fig. ten(c), compound 1-03 types a hydrogen bond with GLU166 (NHO:1.827 and ARG188 (OHO:two.006; the hydrophobic channel is composed of Ala191, Leu167, IL-3 Gene ID Thr190 and His41. Total-score, Crash score and Polar score are 5.65, -1.37 and 1.75, respectively. In Fig. 10(d), compound 1-04 types a hydrogen bond with GLU166 (NH-O:two.123 , and types highly hydrophobic interactions with residues Ala191, Leu167, Phe185, Pro168, and Met165. Total-score, Crash score and Polar score are five.11, -1.33 and 0.84, respectively. It is actually discovered that the created new compound is in very good agreement using the observed biological activity information, and have a higher activity and Total-score, indicating that the compound is successfully designed. three.five. Comparative evaluation of model final results The predicted activity values and residual values of Tomoper CoMFA model and HQSAR model are shown in Table S7. The residual values with the QSAR model of cyclic sulfonamide derivatives are shown in Fig. 11(a) and Fig. 11(b) respectively. Extensive comparison, the Tomoper CoMFA model has smaller residuals than the HQSAR model and is a much better model; compounds 1, 8, 10, 21, 26, 27, 33 and 34 receive the top residual predictions in Topomer CoMFA and HQSAR analysis (residuals 0.02). The two established models have superior internal and external predictive capabilities (Table S8). The results of distinct models is usually verified by each other. Combined using the contour map and colour code map of compound 33, it shows a important area that impacts the inhibition of SARS-CoV-2 by cyclic sulfonamide derivatives. Despite the fact that the two models have obvious variations in structure, the experimental final results and predicted biological activities are consistent, indicati
