Application of the Subtractive Genomics and Molecular Docking Analysis for the Identification of Novel Putative Drug Targets against Salmonella enterica subsp. enterica serovar Poona

Abstract

The emergence of novel pathogenic strains with increased antibacterial resistance patterns poses a significant threat to the management of infectious diseases. In this study, we aimed at utilizing the subtractive genomic approach to identify novel drug targets against Salmonella enterica subsp. enterica serovar Poona strain ATCC BAA-1673. We employed in silico bioinformatics tools to subtract the strain-specific paralogous and host-specific homologous sequences from the bacterial proteome. The sorted proteome was further refined to identify the essential genes in the pathogenic bacterium using the database of essential genes (DEG). We carried out metabolic pathway and subcellular location analysis of the essential proteins of the pathogen to elucidate the involvement of these proteins in important cellular processes. We found 52 unique essential proteins in the target proteome that could be utilized as novel targets to design newer drugs. Further, we investigated these proteins in the DrugBank databases and 11 of the unique essential proteins showed druggability according to the FDA approved drug bank databases with diverse broad-spectrum property. Molecular docking analyses of the novel druggable targets with the drugs were carried out by AutoDock Vina option based on scoring functions. The results showed promising candidates for novel drugs against Salmonella infections.

Subtractive genomics approach in identifying polysacharide biosynthesis protein as novel drug target against Eubacterium nodatum

“…PSORTb [www.psort.org/psortb/] was used for the Protein localization which is used to predict the protein function and genome annotation (Yu et al, 2014). SOUSI [harrier.nagahama-i-bio.ac.jp/sosui/sosui_submit.html] and CELLO [cello.life.nctu.edu.tw] were used to crosscheck the data obtained from PSORTb and proteins were sorted according to their sub-cellular localization (Hossain et al, 2017;Yu et al, 2010). 2D and 3D model development J-Pred4 server (http://www.compbio.dundee.ac.uk/jpred4) was used for prediction of secondary structure of the unique protein targets (Drozdetski et al, 2015).…”

Prioritization of Mur family drug targets against A. baumannii and identification of their homologous proteins through molecular phylogeny, primary sequence, and structural analysis

“…A few studies reported toward the identification, prioritization, and validation of drug target proteins from gram-negative pathogenic bacteria such as Klebsiella pneumonia [16], Salmonella enterica subsp. enterica serovar Poona [17], and Pseudomonas aeruginosa [18] by using different approaches. For computer-aided drug target identification, the Potential Drug Target Database (PDTD) is a very important resource and it is available at http://www.dddc.ac.cn/pdtd/.…”

“…dddc.ac.cn/tarfisdock/) is used as a web server to identify the potential drug targets from the user given small molecule structure based on reverse docking approach. Apart from reverse docking approach, there are several approaches used to identify the drug targets, namely an integrative, multi-omics [16], computational subtractive genomics, molecular docking, virtual screening, [17], structural bioinformatics [15], and protein-protein interaction network [18].…”

Identification of novel drug targets in bovine respiratory disease: an essential step in applying biotechnologic techniques to develop more effective therapeutic treatments

“…For selectivity, subtractive genome analysis has been employed as an important technique and has contributed toward target identification and selection in several pathogens. 32 – 36 This would help to avoid expensive dead-ends when a lead target is identified and investigated in great detail only to discover at a later stage that all its identified inhibitors have off-target effects in the host. This approach paired with the ability to predict essential genes can help to identify potential targets for drug development.…”