Possile Effect of Small Molecule in Hedysari Radix in Antagonizing Tumor Necrosis Factor Receptor 1 Based on Molecular Docking / 中国实验方剂学杂志

ABSTRACT

Objective: To study the effect of small molecule compounds of Hedysari Radix in ntagonizing tumor necrosis factor receptor type 1 (TNFR1) based on molecular docking. Method: The structure of small molecular compound of Hedysari Radix was downloaded from the chemical composition compound library of traditional Chinese medicine, and then optimized to obtain the composition compound library of Hedysari Radix. The three-dimensional structure of the inflammatory target TNFR1 (PDB ID1TNR) was identified. After hydrotreating and anhydrating, the binding pocket residues were identified according to the literature. According to the defined target structure and binding pocket, the flexible molecular docking was conducted between the composition compound library and the target, and the score (Glide Score) was obtained. Based on the results of molecular docking, the first nine small molecular compounds of Glide Score were selected as candidate components. On this basis, the drug-likeness was analyzed, which involved small molecular compounds that meet the number of hydrogen-bonded receptors, the number of hydrogen-bonded donors, the formula weight, the number of rotatable key and the numerical range of lipo-hydro partition coefficient. Finally, the binding mode was analyzed according to pharmacokinetic parameters and complex structure of composition-target docking. Result: The residue set in the TNFR1 drug-binding pocket were identified as glutamic acid109 (Glu109), lysine 35(Lys35), alanine62 (Ala62), serine 74 (Ser74), lysine75 (Lys75), cysteine76 (Cys76), argnine 77(Arg77), glutamine82 (Gln82), threonine89 (Thr89), asparticacid91 (Asp91), argnine92 (Arg92), aspartic acid93 (Asp93), threonine 94(Thr94), valine95 (Val95), cysteine 96(Cys96), argnine104 (Arg104), tyrosine106 (Tyr106), asparagine110 (Asn110), leucine111 (Leu111), phenylalanine112(Phe112), glutamic acid 131(Glu131) and lysine132 (Lys132). Totally 43 small molecular compounds of Hedysari Radix were obtained. Five small molecular compounds, namely hedysari radix, quercetin, isoliquiritin, naringenin, calycosin and liquiritigenin, were screened by comprehensive factors, like docking scoring. Conclusion: Quercetin, isoliquiritin, naringenin, calycosin and liquiritigenin are the effective anti-inflammatory substances of Hedysari Radix, with a great possibility of becoming TNFR1 antagonists.