Insilico structure based drug design approach to find potential hits in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. (July 2022)

• Record Type: Journal Article
• Authors: Damale, Manoj G.; Patil, Rajesh; Ansari, Siddique Akber; Alkahtani, Hamad M.; Ahmed, Sarfaraz; Nur-e-Alam, Mohammad; Arote, Rohidas; Sangshetti, Jaiprakash
• Is Part Of: Computers in biology and medicine. Volume 146(2022)
• Publication Date: 2022-07
• Subjects: Pseudomonas aeruginosa infection -- Tetraacyldisaccharide 4′-kinase -- LpxK -- Lipid a biosynthesis -- Computer-aided drug discovery and design -- Metabolic pathway analysis -- And virtual hits; Medicine -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; 610.285
• DOI: 10.1016/j.compbiomed.2022.105597
• Languages: English
• ISSNs: 0010-4825

Abstract

Abstract: Tetraacyldisaccharide 4′-kinase (LpxK) is the prime enzyme responsible for the biosynthesis of lipid A. LpxK is a key antibacterial drug target, but it is less exploitation in Pseudomonas aeruginosa and other bacterial species limits its therapeutic use. Pseudomonas aeruginosa is responsible for severe infections like pneumonia and urinary tract infections. The precautionary measures of Pseudomonas aeruginosa infections are decisive as it results in extensive drug resistance, systemic bacteremia, and ventilator-associated pneumonia. The current rational approach highlights exploiting the use of computer-aided drug design approaches to counter Pseudomonas aeruginosa specific LpxK. The various approaches used were exploring the metabolic pathway database (Metacyc), drug target validation using DEG, protein modeling, ligand docking, e-pharmacophore assisted virtual screening, physicochemical and Toxicity profile prediction studies, and molecular simulations in spotting out novel potential hits compounds. The virtual hits which have highly ranked in the study were STOCK4S-16119, STOCK1S −60869, STOCK6S −43621, STOCK6S −3328, and STOCKS-39 892 which can act as a scaffold for the establishment of new hits against LpxK and can result in control of Pseudomonas aeruginosa infectivity. Graphical abstract: Image 1 Highlights: A rational approach in computer aided drug design. It explores DEG, protein modeling, ligand docking. Toxicity profile predication studies using virtual screening. Identifying Potential hits using Molecular simulations.