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Understanding the binding conformation of ceftolozane/tazobactam with Metallo‐β‐lactamases VIM ‐5 and IMP ‐7 of Pseudomonas aeruginosa : A molecular docking and virtual screening process
Author(s) -
Kullappan Malathi,
Ambrose Jenifer,
Surapaneni Krishna Mohan
Publication year - 2021
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2898
Subject(s) - virtual screening , autodock , pseudomonas aeruginosa , docking (animal) , tazobactam , antibiotics , microbiology and biotechnology , antibiotic resistance , drug resistance , chemistry , biology , pharmacology , bacteria , in silico , drug discovery , medicine , biochemistry , gene , genetics , imipenem , nursing
Pseudomonas aeruginosa ( P . aeruginosa ) is one of the community‐acquired and healthcare‐associated infections causing organisms. It has become resistant to most of the available antibiotics and is termed multi‐drug resistance (MDR). There are a limited number of antibiotics are available to treat such MDR organism causing infections. The ceftolozane/tazobactam is one among the combination drug therapy (CDT) prescribed for the treatment of MDR causing infections. The resistance for the same CDT was observed in the MDR P . aeruginosa harboring VIM‐5 and IMP‐7 Metallo beta (β)‐lactamases (MBLs). To explore the resistance mechanism at the molecular level, docking studies were carried out for antibiotics against VIM‐5 and IMP‐7 MBLs. The Zn2 metal ions carry out the nucleophile attack on the carbonyl carbon of the β‐lactam ring along with conserved water molecules. To find lead compounds against the MBLs, a virtual screening process was carried out. We have employed MODELLER for structure modeling, AutoDock for molecular docking and AutoDock Vina, Molinspiration, PASS prediction & admetSAR in virtual screening. The search of low binding energy ceftolozane analogs against VIM‐5 and IMP‐7 MBLs has resulted in the ZINC000029060075 and ZINC9163636 analogs. Similarly, the screening of high binding energy inhibitors against VIM‐5 and IMP‐7 MBLs has resulted in ZINC3831503 and ZINC897247 tazobactam analogs respectively. The ADMET prediction results in the non‐toxicity of the lead compounds. Our study may provide new insights for the scientist who are designing novel drugs against MDR P . aeruginosa causing infections.