Comparative Molecular docking analysis of DNA Gyrase subunit A in Pseudomonas aeruginosaPAO1.

Aman Gupta,Ashish Kumar Tewari,Sanjeev Kumar Sharma,Ashwani Mathur,Chakresh Kumar Jain,Vipul Surenderkumar,Vanashika Sharma,Gulshan Wadhwa

doi:10.6026/97320630009116

Abstract

Pseudomonas aeruginosa is an opportunistic bacterium known for causing chronic infections in cystic fibrosis and chronic obstructive pulmonary disease (COPD) patients. Recently, several drug targets in Pseudomonas aeruginosa PAO1 have been reported using network biology approaches on the basis of essentiality and topology and further ranked on network measures viz. degree and centrality. Till date no drug/ligand molecule has been reported against this targets.In our work we have identified the ligand /drug molecules, through Orthologous gene mapping against Bacillus subtilis subsp. subtilis str. 168 and performed modelling and docking analysis. From the predicted drug targets in PA PAO1, we selected those drug targets which show statistically significant orthology with a model organism and whose orthologs are present in all the selected drug targets of PA PAO1.Modeling of their structure has been done using I-Tasser web server. Orthologous gene mapping has been performed using Cluster of Orthologs (COGs) and based on orthology; drugs available for Bacillus sp. have been docked with PA PAO1 protein drug targets using MoleGro virtual docker version 4.0.2.Orthologous gene for PA3168 gyrA is BS gyrAfound in Bacillus subtilis subsp. subtilis str. 168. The drugs cited for Bacillus sp. have been docked with PA genes and energy analyses have been made. Based on Orthologous gene mapping andin-silico studies, Nalidixic acid is reported as an effective drug against PA3168 gyrA for the treatment of CF and COPD.

Highlights

Pseudomonas aeruginosa (PA) is a gram negative, rod-shaped and opportunistic bacterium known for causing chronic infections in cystic fibrosis and chronic obstructive pulmonary disease (COPD) patients [1]
Drugs have been found for PA3168 (DNA Gyrase subunit A), PA0004 (DNA Gyrase subunit B), and PA3987 based on orthologous genes found in Bacillus subtilis subsp. subtilis str
Nalidixic Acid is reported as an excellent inhibitor for Gyrase A in Bacillus sp. and have been found to show comparable energies and hydrogen bonding levels in PA PAO1 orthologous gene PA3168 while the docking results of target PA3168 drug target of PA PAO1 with other drug molecules namely 2-hydroxyquinoline, Oxolinic Acid, Norfloxacin and Ciprofloxacin cited for BS gyr A of Bacillus subtilis subsp. subtilis str.168 were not comparable

Summary

Introduction

Pseudomonas aeruginosa (PA) is a gram negative, rod-shaped and opportunistic bacterium known for causing chronic infections in cystic fibrosis and chronic obstructive pulmonary disease (COPD) patients [1]. Its mode of action involves adherence to tissue surface using its pili, flagellum and exo-S and replication to form a mass of cells. The bacterium gradually synthesizes biofilm for its prolonged attachment with host tissues and by its virulent factors causes severe tissue damage. The bio films protect these bacteria from adverse environmental factors, raised a serious problem for medical care in industrialised societies, especially for immune-compromised patients and the elderly [2]. PA is capable of acquiring resistance genes and shows multiple drug resistance. The increasing number of multi drug resistant PA (MDRPA) strains has rendered many existing drugs as ineffective, including the most powerful anti-pseudomonal beta-lactams [1]

Methods

Conclusion