Comparative study for druggable target finding and drug designing against strains of human pathogen Streptococcus pyogens using various computational tools

The project aims to find the druggable targets from the bacteria Streptococcus pyogenes strains using subtractive genomics approach so that comparative study can be held between the strains. These druggable target identification will help to design drug against deadly human pathogen S.

Project Title

Comparative study for druggable target finding and drug designing against strains of human pathogen Streptococcus pyogens using various computational tools

Project Area of Specialization

Artificial Intelligence

Project Summary

The project aims to find the druggable targets from the bacteria Streptococcus pyogenes strains using subtractive genomics approach so that comparative study can be held between the strains. These druggable target identification will help to design drug against deadly human pathogen S. pyogenes. It will mainly include the use of different freely available online bioinformatics tools. The step wise procedure to be followed is:

1. Retrieval of proteome from UniProt

The complete proteome of all strains will be retrieved from ExPASy server in UniProtKB format including FASTA file and Excel sheet.

2. Paralog removal using CD-HIT

Paralogous protein sequences will be removed using CD-HIT with the cut-off value of 0.6 (60%). The identified paralogous sequences will then be screened out from complete proteome of pathogen obtained from ExPASy.

3. Homolog removal against host proteome

Homologous proteins will be removed from non paralogous sequences of pathogen using BLASTp against RefSeq Human.

4. Essential gene finding of pathogen

Database of Essential Gene (DEG) will be utilized to find out the essential genes of pathogen as this database covers curated information regarding the proteins expressed by essential genes.

5. Pathway analysis of Host and Pathogen

Kyoto Encyclopedia of Genes and Genomes (KEGG) database will be used to find metabolic pathways of human and pathogen. KEGG Automated Annotation Server (KAAS) present on KEGG will be utilized for this purpose which show results in form of KEGG Orthology list assignment, enzyme name, Enzyme Commission (EC) number etc.

6. Protein localization and functional family prediction

The protein specific to pathogen involved in basic metabolic pathway of pathogen and not present in human will be utilized further for the localization finding and functional family prediction. Localization will be used to determine the drug type whether that will be vaccine or medicine.

7. Druggable target identification

Druggable targets will be checked among the screened list of proteins using BLASTp against DrugBank database. The protein to be used further for drug designing will be selected after checking their potency.

8. Structure finding/Model building

The three dimensional (3D) structure of selected druggable target will be searched in RCSB Protein Data Bank (PDB). If 3D structure will not be present than we will use Homology Modelling, Ab-Initio and Threading method to predict 3D model of protein.

9. Active Site prediction

Various computational methods have been developed to explore the local secondary structures of protein and depict active site residues. One such method is Multiple Sequence Alignment (MSA) which will be used in our study along-with literature survey.

10. Docking of druggable target with ligands

Druggable target will be docked with library of ligands to find best docked ligand using different tools such as AutoDcok.

Project Objectives

The project is designed for following objectives:

1.  Better insight into disease mechanism of human pathogen

2. Better understanding of multiple drug resistance mechanism of pathogen.

3. Finding of plausible druggable targets for pathogen.

4. Drug designing against pathogen.

5. Vaccine target identification.

Project Implementation Method

Druggable targets will be used further for drug development against pathogen. The developed drug will be utilized further for the purpose of laboratory and clinical trials.

Benefits of the Project

Following benefits will be achieved by this project:

1. the disease mechanism of pathogen against host will be better understandable.

2. reasons of pathogen’s multiple drug resistance will be studied well.

3. Druggable targets identified through this study will be essential proteins for the pathogen.

4. drugs which will be harmless for human-host will be designed so that they can act on pathogen affectively without causing any harm to host.

5. The proteins which will be membranous would come out to be better option for vaccine targets.

Technical Details of Final Deliverable

The druggable targets: the essential proteins of pathogen which will be present in unique pathway of pathogen will be identified. These targets will act as binding sites for the drugs.

Designed drug: these drugs will be identified to be best docked ligands out of the library of ligands. These drugs can be further developed for the purpose of laboratory and clinical trials.

Vaccine targets: the essential membranous proteins of pathogen present in unique metabolic pathway will be further used as the vaccine targets.

Final Deliverable of the Project

HW/SW integrated system

Type of Industry

Medical

Technologies

Others

Sustainable Development Goals

Good Health and Well-Being for People

Required Resources

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