scholarly journals Deciphering Potential Drug Targets in Clostridium Perfringens through Metabolic Pathway Analysis

2019 ◽  
pp. 432-437
Author(s):  
M Arockiyajainmary ◽  
Sivashankari Selvarajan
Keyword(s):  
Clostridium Perfringens ◽  
Pathway Analysis ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Cellular Localization ◽  
Potential Drug ◽  
Metabolic Pathway Analysis ◽  
Homologous Proteins ◽  
Potential Drug Targets

Background: In our day-to-day life, we are facing many dreadful diseases caused by many infectious pathogens. These pathogens invade the living organisms (host) and lethally damaging them. These dreadful pathogens were also be used as bioweapons. Among them, Clostridium perfringens is taken for the study. Clostridium perfringens is an anaerobic, rod shaped, gram positive bacteria capable of forming spores. It is prevalent in the environment and in the intestine of humans and other animals. It is the causative agent for a wide range of diseases including food borne diseases, gas gangrene and flesh eating disease called necrotizing fasciitis. C. perfringens is commonly found on raw meat and poultry that espouse to grow in conditions with very little or no oxygen, and under ideal conditions can multiply very rapidly. These conditions are occasionally lethal due to the substantial number of toxins such as alpha toxin, beta toxin, epsilon toxin and iota toxin produced by C. perfringens. It is significantly important to analyze the Drug targets of the pathogen in order to destroy them. Objective: The present work aims in identifying potential drug targets in C. perfringens through metabolic pathway analysis. Method: Primarily, the metabolic pathways of the host and pathogen are compared to identify unique pathways in the bacteria. Among the enzymes that catalyze unique metabolic pathways, the essential ones for the survival of the pathogen are identified. The druggability of the essential enzymes are predicted through identification of its sub cellular localization and other druggable parameters. Results: The comparative metabolic pathway analysis result shows that, among the 98 metabolic pathways of C.perfringens, 25 pathways were unique that they did not have a counterpart with Human. There were 113 enzymes involved in these unique pathways. The NCBI’s protein Blast search against human was done to identify the non-homologous proteins. There were 93 non-homologous proteins. Among the 93 non-homologous proteins, 47 proteins were found to be essential. Based on their sub-cellular localization, 32 proteins were identified as potential drug targets and 15 are probable vaccine candidates. Conclusion: The present work which started with 25 different pathways with more than a hundred different enzymes, resulted in the identification of 32 putative drug targets against C.perfringens infection. All these 32 identified targets did not have any human homolog and are highly essential for the survival of the organism. They were concluded as potential drug targets. Designing of compounds to inhibit these enzymes would be successful for treating the life threatening infections caused by this pathogen.

scholarly journals “In Silico Metabolic Pathway Analysis and Docking Analysis of Treponema Pallidum Subs. Pallidum Nichols for Potential Drug Targets”

2017 ◽  
Vol 10 (5) ◽  
pp. 261
Author(s):  
Radha Mahendran
Keyword(s):  
Homology Modeling ◽  
Metabolic Pathway ◽  
Drug Targets ◽  
Active Sites ◽  
Homo Sapiens ◽  
Treponema Pallidum ◽  
Potential Drug ◽  
Metabolic Pathway Analysis ◽  
Docking Analysis ◽  
Potential Drug Targets

ABSTRACT Objective: Syphilis is a sexually transmitted infection caused by the spirochaete, Treponema pallidum subspecies pallidum nichols. In this study, a comparative metabolic pathway analysis and molecular docking was performed to identify putative drug targets.Methods: The biochemical pathways of Treponema pallidum subs. pallidum nichols and Homo sapiens were compared using KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway. The amino acid sequence of the selected enzymes were retrieved and Blastp was performed. Out of 9 enzymes, enolase was modeled using ModWeb and the structure was validated using RAMPAGE. The active sites were identified using Metapocket 2.0 and further docked using AutoDock 4.2.Results: The enzymes which were not similar to that of Homo sapiens were filtered out as potential drug targets. A total of 9 enzymes were retrieved which were present only in the Treponema pallidum subs. pallidum nichols. The structure obtained from Homology modeling was validated and further active sites were predicted. The docking analysis results showed the interaction between enolase and doxycycline and the structures were obtained using PyMol.Conclusion: Through this study, doxycycline which has antibacterial effect and a derivative of tetracycline could be one of the potential ligands. Keywords: Syphilis, Treponema pallidum, KEGG, Blastp, metabolic pathway, Homology Modeling, DockingREVIEWERSProf.G.SHOBA,Bioinformatics Department      Dr.M.G.R Janaki College of Arts and Science for Women      University of Madras      [email protected]      Phone: 9094009791 2. Prof .VINOTH,Biotechnology & Bioinformatics DepartmentHindustan University,Kelambakkam, Chennai-603103                  [email protected]                 Phone - + 91 97895 95766

METABOLIC PATHWAY ANALYSIS OFS. PNEUMONIAE: ANIN SILICOAPPROACH TOWARDS DRUG-DESIGN

2007 ◽  
Vol 05 (01) ◽  
pp. 135-153 ◽  
Author(s):  
SHAILZA SINGH ◽  
B. K. MALIK ◽  
D. K. SHARMA
Keyword(s):  
Drug Design ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Nucleotide Metabolism ◽  
Rational Drug Design ◽  
Systematic Evaluation ◽  
Potential Drug ◽  
Genome Database ◽  
Potential Drug Targets

The emergence of multidrug resistant varieties of Streptococcus pneumoniae (S. pneumoniae) has led to a search for novel drug targets. An in silico comparative analysis of metabolic pathways of the host Homo sapiens (H. sapiens) and the pathogen S. pneumoniae have been performed. Enzymes from the biochemical pathways of S. pneumoniae from the KEGG metabolic pathway database were compared with proteins from the host H. sapiens, by performing a BLASTp search against the non-redundant database restricted to the H. sapiens subset. The e-value threshold cutoff was set to 0.005. Enzymes, which do not show similarity to any of the host proteins, below this threshold, were filtered out as potential drug targets. Five pathways unique to the pathogen S. pneumoniae when compared to the host H. sapiens have been identified. Potential drug targets from these pathways could be useful for the discovery of broad-spectrum drugs. Potential drug targets were also identified from pathways related to lipid metabolism, carbohydrate metabolism, amino acid metabolism, energy metabolism, vitamin and cofactor biosynthetic pathways and nucleotide metabolism. Of the 161 distinct targets identified from these pathways, many are in various stages of progress at the Microbial Genome Database. However, 44 of the targets are new and can be considered for rational drug design. The study was successful in listing out potential drug targets from the S. pneumoniae proteome involved in vital aspects of the pathogen's metabolism, persistence, virulence and cell wall biosynthesis. This systematic evaluation of metabolic pathways of host and pathogen through reliable and conventional bioinformatics approach can be extended to other pathogens of clinical interest.

scholarly journals IN SILICO IDENTIFICATION OF NOVEL DRUG TARGETS IN ACINETOBACTER BAUMANNII BY SUBTRACTIVE GENOMIC APPROACH

2018 ◽  
Vol 11 (3) ◽  
pp. 230 ◽  
Author(s):  
Meenu Goyal ◽  
Citu Citu ◽  
Nidhi Singh
Keyword(s):  
Acinetobacter Baumannii ◽  
In Silico ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Potential Drug ◽  
Homologous Proteins ◽  
Essential Proteins ◽  
Novel Drug ◽  
Potential Drug Targets ◽  
Novel Drug Targets

 Objective: Multiple drug resistance (MDR) in bacteria, particularly Gram-negative bacilli, has significantly hindered the treatment of infections caused by these bacteria. This results in the need for identifying new drugs and drug targets for these bacteria. The objective of this study was to identify novel drug targets in Acinetobacter baumannii which has emerged as a medically important pathogen due to an increasing number of infections caused by it and its MDR property.Methods: In our study, we implemented in silico subtractive genomics approach to identify novel drug targets in A. baumannii American type culture collection 17978. Various databases and online software were used to build a systematic workflow involving comparative genomics, metabolic pathways analysis, and drug target prioritization to identify pathogen-specific novel drug targets.Results: First, 458 essential proteins were retrieved from a database of essential genes, and by performing BLASTp against Homo sapiens, 246 human non-homologous essential proteins were selected of 458 proteins. Metabolic pathway analysis performed by Kyoto Encyclopedia of Genes and Genomes–Kyoto Automatic Annotation Server revealed that these 246 essential non-homologous proteins were involved in 66 metabolic pathways. Among these metabolic pathways, 12 pathways were found to be unique to Acinetobacter that involved 37 non-homologous essential proteins. Of these essential non-homologous proteins, 19 proteins were found in common as well as unique metabolic pathways and only 18 proteins were unique to Acinetobacter. Finally, these target proteins were filtered to 9 potential targets, based on subcellular localization and assessment of druggability using Drug bank, ChEMBL, and literature.Conclusion: Our study identified nine potential drug targets which are novel targets in A. baumannii and can be used for designing drugs against these proteins. These drugs will be pathogen specific with no side effects on human host, as the potential drug targets are human non-homologous.

scholarly journals Modeling Novel Putative Drugs and Vaccine Candidates against Tick-Borne Pathogens: A Subtractive Proteomics Approach

2020 ◽  
Vol 7 (3) ◽  
pp. 129
Author(s):  
Abid Ali ◽  
Shabir Ahmad ◽  
Abdul Wadood ◽  
Ashfaq U. Rehman ◽  
Hafsa Zahid ◽  
...  
Keyword(s):  
Drug Targets ◽  
Effective Control ◽  
Potential Drug ◽  
Homologous Proteins ◽  
Vaccine Candidates ◽  
Target Proteins ◽  
Subtractive Proteomics ◽  
Novel Drug ◽  
Potential Drug Targets ◽  
Novel Drug Targets

Ticks and tick-borne pathogens (TBPs) continuously causing substantial losses to the public and veterinary health sectors. The identification of putative drug targets and vaccine candidates is crucial to control TBPs. No information has been recorded on designing novel drug targets and vaccine candidates based on proteins. Subtractive proteomics is an in silico approach that utilizes extensive screening for the identification of novel drug targets or vaccine candidates based on the determination of potential target proteins available in a pathogen proteome that may be used effectively to control diseases caused by these infectious agents. The present study aimed to investigate novel drug targets and vaccine candidates by utilizing subtractive proteomics to scan the available proteomes of TBPs and predict essential and non-host homologous proteins required for the survival of these diseases causing agents. Subtractive proteome analysis revealed a list of fifteen essential, non-host homologous, and unique metabolic proteins in the complete proteome of selected pathogens. Among these therapeutic target proteins, three were excluded due to the presence in host gut metagenome, eleven were found to be highly potential drug targets, while only one was found as a potential vaccine candidate against TBPs. The present study may provide a foundation to design potential drug targets and vaccine candidates for the effective control of infections caused by TBPs.

scholarly journals A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information

2009 ◽  
Vol 104 (8) ◽  
pp. 1100-1110 ◽  
Author(s):  
Marcelo Alves-Ferreira ◽  
Ana Carolina Ramos Guimarães ◽  
Priscila Vanessa da Silva Zabala Capriles ◽  
Laurent E Dardenne ◽  
Wim M Degrave
Keyword(s):  
Pathway Analysis ◽  
Metabolic Pathway ◽  
In Silico ◽  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Metabolic Pathway Analysis ◽  
Drug Target Discovery ◽  
New Approach ◽  
Genome Information
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