lar structure fragments), the topomer approach is utilised to compare and obtain the molecular fragments with similarity. The Topomer Distance (TOPDIST) plus the contribution worth of substituents are integrated and the established Topomer CoMFA model scores these fragments and performs virtual screening on the cleaved fragments toJ.-B. TONG, X. ZHANG, D. LUO et al.Chinese Journal of Analytical IKKε Formulation Chemistry 49 (2021) 63Fig. 4. (a): Prototype molecular generation diagram (Green location represents prototype molecule). (b): Compound 33 interacts using the active web site of protein 7JYC.acquire R1 , R2 and R3 substituents with greater contribution worth. Then, SARS-CoV-2 inhibitor compact molecules with far better activity are obtained by splicing style. two.7. Molecular docking study Molecular docking is amongst the most frequently utilized approaches to study the mutual recognition course of action of geometric matching and energy matching in drug style. The principle of molecular docking would be the “lock and important model” [33]. The lock is usually a macromolecular receptor with different structures, and the key is really a compact molecule ligand using a precise structure. When the macromolecular receptor as well as the smaller molecule ligand are complementary and matched in geometry, the electrostatic interactions, hydrogen bond interactions and hydrophobic interactions will take place. Then, in the process of binding, the conformation of the compact molecule ligand and its surrounding amino acid conformation steadily adjust, adapt to one another and induce fit. So that you can exert its inhibitory activity against SARS-CoV-2, cyclic sulfonamide compounds need to have specific affinity with SARS-CoV2 enzyme protein. After the two are sufficiently close to each other, they are going to combine with one another and interact with each other by way of proper conformational adjustment, finally forming a D4 Receptor custom synthesis steady complicated conformation [34]. Surflex-Dock takes polarity impact, hydrophobic effect and hydrogen bond impact into account to score the interaction involving ligand and receptor, as well as the Total score is definitely the dissociation constant (representing docking activity). We use SYBYL-X 2.0 (SurflexDock approach) and Discovery Studio Visualization tool 2017 to study the molecular docking from the least active compound(two, 3, 7, eight, 25, 26, 27, 29) as well as the most active compound 33 using the 7JYC protein around the information set reported in the earlier experimental studies to additional analyze and verify the molecular structure of cyclic sulfonamide compounds [35]; and by way of the comparison on the two approaches, the reason why compound 33 features a larger inhibitory activity against SARS-CoV-2 is explained. Ultimately, the 4 newly designed inhibitor molecules are docked to understand the antiviral mechanism in the developed compound. The three-dimensional crystal structure of protease (7JYC) comes from the PDB database (http://rcsb.org/). Ahead of molecular docking, the protein receptor molecules are pretreated, the required little molecule ligands are extracted in the macromolecular complexes, and the own ligands, metal ions, water molecules, as well as other residues and terminal residues of protein are removed. Polar hydrogen and point charges are added to expose the binding pocket (represented by the prototype molecule) [36]. The binding pocket is filled with hydrogen bond donors, hydrogen bond acceptors and hydrophobic web site molecular probes. The interaction mode in the processed prototype little molecule and protein macromolecule is shown in Fig. four(a). The crystal structur