Novel Hybrid Virtual Screening Protocol Based on Molecular Docking and Structure-Based Pharmacophore for Discovery of Methionyl-tRNA Synthetase Inhibitors as Antibacterial Agents

International Journal of Molecular Sciences

Chi Liu³  Gu He³  Qinglin Jiang¹  Bo Han² 

[1] Department of Pharmacy, Chengdu Medical College, Chengdu 610083, Sichuan, China;State Key Laboratory Breeding Base of Systematic research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; E-Mails:;State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; E-Mail:

关键词: pharmacophore;    molecular docking;    methionyl-tRNA synthetase;    virtual screening;   

DOI  :  10.3390/ijms140714225

来源: mdpi

【 摘 要 】

Methione tRNA synthetase (MetRS) is an essential enzyme involved in protein biosynthesis in all living organisms and is a potential antibacterial target. In the current study, the structure-based pharmacophore (SBP)-guided method has been suggested to generate a comprehensive pharmacophore of MetRS based on fourteen crystal structures of MetRS-inhibitor complexes. In this investigation, a hybrid protocol of a virtual screening method, comprised of pharmacophore model-based virtual screening (PBVS), rigid and flexible docking-based virtual screenings (DBVS), is used for retrieving new MetRS inhibitors from commercially available chemical databases. This hybrid virtual screening approach was then applied to screen the Specs (202,408 compounds) database, a structurally diverse chemical database. Fifteen hit compounds were selected from the final hits and shifted to experimental studies. These results may provide important information for further research of novel MetRS inhibitors as antibacterial agents.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland