lar structure fragments), the topomer method is utilised to evaluate and find the molecular fragments with similarity. The Topomer Distance (TOPDIST) along with the contribution worth of substituents are integrated and the established Topomer CoMFA model scores these fragments and performs virtual screening around the cleaved fragments toJ.-B. TONG, X. ZHANG, D. LUO et al.Chinese Journal of Analytical Chemistry 49 (2021) 63Fig. four. (a): Prototype molecular generation diagram (Green area represents prototype molecule). (b): Compound 33 interacts with the active web-site of protein 7JYC.receive R1 , R2 and R3 substituents with greater contribution value. Then, SARS-CoV-2 inhibitor compact molecules with better activity are obtained by splicing style. two.7. Molecular docking study Molecular docking is one of the most usually employed procedures to study the mutual recognition procedure of geometric matching and power matching in drug design and style. The principle of molecular docking could be the “lock and key model” [33]. The lock is usually a macromolecular receptor with ATM Compound various structures, plus the key is really a little molecule ligand having a distinct structure. When the macromolecular receptor and the little molecule ligand are complementary and matched in geometry, the electrostatic interactions, hydrogen bond interactions and hydrophobic interactions will occur. Then, within the course of action of binding, the conformation with the little molecule ligand and its surrounding amino acid conformation steadily transform, adapt to each other and induce fit. In an effort to exert its inhibitory activity against SARS-CoV-2, cyclic sulfonamide compounds want to have specific affinity with SARS-CoV2 enzyme protein. Just after the two are sufficiently close to one another, they will combine with one another and interact with one another by way of suitable conformational adjustment, ultimately forming a steady complex conformation [34]. Surflex-Dock requires polarity impact, hydrophobic impact and hydrogen bond effect into account to score the interaction involving ligand and receptor, as well as the Total score may be the dissociation constant (representing docking activity). We use SYBYL-X two.0 (SurflexDock technique) and Discovery Studio Visualization tool 2017 to study the molecular docking of the least active compound(two, 3, 7, 8, 25, 26, 27, 29) and the most active compound 33 with the 7JYC protein around the information set reported in the prior experimental research to further analyze and confirm the molecular structure of cyclic sulfonamide compounds [35]; and through the comparison with the two methods, the purpose why compound 33 has a larger inhibitory activity against SARS-CoV-2 is explained. Ultimately, the four newly designed inhibitor molecules are docked to know the antiviral mechanism from the developed compound. The three-dimensional crystal structure of protease (7JYC) comes in the PDB ACAT1 Synonyms database (http://rcsb.org/). Just before molecular docking, the protein receptor molecules are pretreated, the essential small molecule ligands are extracted from the macromolecular complexes, as well as the personal ligands, metal ions, water molecules, along with 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 website molecular probes. The interaction mode with the processed prototype tiny molecule and protein macromolecule is shown in Fig. four(a). The crystal structur
