Virtual Screening of DNA Topoisomerase Ⅳ Inhibitors Based on Molecular Docking
XU Ming-xin1,2, CHEN Shuang-kou1,2*, TAN Xiao-qing1,2, REN Feng-ming3, GUAN Tian-bing1,2
1. Chongqing Key Laboratory of Industrial Fermentation Microorganism (Chongqing University of Science and Technology), Chongqing 401331, China; 2. Department of Chemistry and Chemical Engineering, Chongqing University of Science and Technology, Chongqing 401331, China; 3. Institute of Medicinal Plant Cultivation, Chongqing 408435, China
Abstract：OBJECTIVE To screen DNA topoisomerase Ⅳ inhibitors by virtual screening based on molecular docking and in vitro bacteriostatic test. METHODS Methodological research was performed to study the target proteins of 1S16, 3FV5 and 4ZH0 of DNA topoisomerase Ⅳ through the AutoDock Vina program. The molecular docking models with strong enrichment ability for active molecules were evaluated by parameters of RMSD, AUC and EF value, and the model was used to conducte large-scale virtual screening of the database. Compounds with binding energy below the threshold value were retained for in vitro bacteriostatic test. RESULTS Based on the comprehensive retrospective verification results, it was found that the molecular docking model of the 1S16 target protein had a strongest ability to enrich active molecules. Based on this model, 22 compounds with potential bacteriostatic activity were virtually screened, and 8 of them were found to have obvious anti-Escherichia coli activity in vitro bacteriostatic test. CONCLUSION In this study, the theoretical calculation method combined with the experimental results showed that 8 compounds have clear anti-Escherichia coli activity, which are expected to be the novel DNA topoisomerase Ⅳ inhibitors.
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2023, Vol. 58 
