Pharmacoinformatics approaches to identify potential hits against tetraacyldisaccharide 4'-kinase (LpxK) of Pseudomonas aeruginosa .
Manoj G DamaleShahebaaz K PathanRajesh B PatilJaiprakash N SangshettiPublished in: RSC advances (2020)
Pseudomonas aeruginosa infection can cause pneumonia and urinary tract infection and the management of Pseudomonas aeruginosa infection is critical in multidrug resistance, hospital-acquired bacteremia and ventilator-associated pneumonia. The key enzymes of lipid A biosynthesis in Pseudomonas aeruginosa are promising drug targets. However, the enzyme tetraacyldisaccharide 4'-kinase (LpxK) has not been explored as a drug target so far. Several pharmacoinformatics tools such as comparative metabolic pathway analysis (Metacyc), data mining from a database of essential genes (DEG), homology modeling, molecular docking, pharmacophore based virtual screening, ADMET prediction and molecular dynamics simulation were used in identifying novel lead compounds against this target. The top virtual hits STOCK6S-33288, 43621, 39892, 37164 and 35740 may serve as the templates for the design and synthesis of potent LpxK inhibitors in the management of serious Pseudomonas aeruginosa infection.
Keyphrases
- pseudomonas aeruginosa
- molecular docking
- molecular dynamics simulations
- cystic fibrosis
- biofilm formation
- acinetobacter baumannii
- urinary tract infection
- healthcare
- electronic health record
- intensive care unit
- tyrosine kinase
- gene expression
- protein kinase
- staphylococcus aureus
- multidrug resistant
- extracorporeal membrane oxygenation
- human health
- acute respiratory distress syndrome
- transcription factor
- cell wall