Pharmacoinformatics approaches to identify potential hits against tetraacyldisaccharide 4 '-kinase (LpxK) ofPseudomonas aeruginosa

摘要

Pseudomonas aeruginosainfection can cause pneumonia and urinary tract infection and the management ofPseudomonas aeruginosainfection is critical in multidrug resistance, hospital-acquired bacteremia and ventilator-associated pneumonia. The key enzymes of lipid A biosynthesis inPseudomonas aeruginosaare 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 seriousPseudomonas aeruginosainfection.