In silico identification of potential inhibitors targeting Streptococcus mutans sortase A  

作　　者：Hao Luo Dan-Feng Liang Min-Yue Bao Rong Sun Yuan-Yuan Li Jian-Zong Li Xin Wang Kai-Min Lu Jin-Ku Bao 

机构地区：[1]School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment,Sichuan University [2]State Key Laboratory of Biotherapy/Collaborative Innovation Centre for Biotherapy,West China Hospital,Sichuan University [3]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University

出　　处：《International Journal of Oral Science》2017年第1期53-62,共10页国际口腔科学杂志（英文版）

基　　金：supported in part by the National Natural Science Foundation of China (Nos 31300674,81173093,30970643,81373311 and J1103518);the Special Programme for Youth Science and the Technology Innovative Research Group of Sichuan Province,China (No 2011JTD0026)

摘　　要：Dental caries is one of the most common chronic diseases and is caused by acid fermentation of bacteria adhered to the teeth. Streptococcus mutans （S. mutans） utilizes sortase A （SrtA） to anchor surface proteins to the cell wall and forms a biofilm to facilitate its adhesion to the tooth surface. Some plant natural products, especially several flavonoids, are effective inhibitors of SrtA. However, given the limited number of inhibitors and the development of drug resistance, the discovery of new inhibitors is urgent. Here, the high-throughput virtual screening approach was performed to identify new potential inhibitors of S. mutans SrtA. Two libraries were used for screening, and nine compounds that had the lowest scores were chosen for further molecular dynamics simulation, binding free energy analysis and absorption, distribution, metabolism, excretion and toxicity （ADMET） properties analysis. The results revealed that several similar compounds composed of benzofuran, thiadiazole and pyrrole, which exhibited good affinities and appropriate pharmacokinetic In addition, the carbonyl of these compounds can have a strategy for microbial infection disease therapy. parameters, were potential inhibitors to impede the catalysis of SrtA. key role in the inhibition mechanism. These findings can provide a newDental caries is one of the most common chronic diseases and is caused by acid fermentation of bacteria adhered to the teeth. Streptococcus mutans （S. mutans） utilizes sortase A （SrtA） to anchor surface proteins to the cell wall and forms a biofilm to facilitate its adhesion to the tooth surface. Some plant natural products, especially several flavonoids, are effective inhibitors of SrtA. However, given the limited number of inhibitors and the development of drug resistance, the discovery of new inhibitors is urgent. Here, the high-throughput virtual screening approach was performed to identify new potential inhibitors of S. mutans SrtA. Two libraries were used for screening, and nine compounds that had the lowest scores were chosen for further molecular dynamics simulation, binding free energy analysis and absorption, distribution, metabolism, excretion and toxicity （ADMET） properties analysis. The results revealed that several similar compounds composed of benzofuran, thiadiazole and pyrrole, which exhibited good affinities and appropriate pharmacokinetic In addition, the carbonyl of these compounds can have a strategy for microbial infection disease therapy. parameters, were potential inhibitors to impede the catalysis of SrtA. key role in the inhibition mechanism. These findings can provide a new

关 键 词：dental caries molecular dynamics simulation molecular docking potential inhibitors sortase A Streptococcus mutans 

分 类 号：R781.1[医药卫生—口腔医学]