In-silico Drug designing
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The document outlines the process of drug designing for tuberculosis, covering various aspects such as target identification, validation, structure retrieval, and final model development using computational methods. It details the steps involved in creating a prospective drug, including ligand binding affinity analysis and biosafety considerations. Additionally, it provides references to software and resources used throughout the drug design process.
In-silico Drug designing
- 2. Various sectors of IBI:
- 3. CONTENTS: Drug designing Tuberculosis - an overview Target Identification Target Validation Structure Retrieval Structure Validation Final Model Active Site Identification Lead Identification
- 4. Lead Insertion In Active Site Development Of Lead In Active Site Docking Proposal to Final Molecule Bibliography
- 5. Drug Designing: Drug designing is a process used in biopharmaceutical industry to discover and develop new drug compounds. Variety of computational methods are used to identify novel compounds ,design compounds for selectivity and safety. Structure-based drug design, ligand-based drug design , homology based methods are used depending on how much information is available about drug targets and potential drug compounds.
- 6. Tuberculosis: Tuberculosis is a infectious disease caused by various strains of mycobacteria ,usually mycobacterium tuberculosis. Tuberculosis typically attacks the lungs , but can also affect other parts of the body. It is spread through the air when the people who have an active TB infection cough , sneeze or otherwise transmit their saliva through air.
- 7. Chest X-ray:infetion in lungs
- 8. Symptoms of active TB: Chronic cough Fever Night Sweats Blood-tinged sputum Unusual weight loss
- 9. TARGET IDENTIFICATION: A “DRUG TARGET” is a key molecule involved in a particular metabolic and signaling pathway that is specific to disease condition and pathology , or to the infectivity or survival of a microbial pathogen. Some steps are involved: search for all the molecules ,enzymes and proteins involved in disease. Found all these sequence on :http//www.ncbi.nlm.nih.gov Got the sequences in FASTA format
- 10. TARGET VALIDATION: Perform the protein blast for all the genes/proteins w.r.t homosapiens . Select the least matching molecule in human and again perform the BLAST now in protein(sub-heading) category. As the query sequence matched best with Rv0554 , so we selected our target molecule and its structure can be obtained from RCSB(The Research Collaboratory for Structural Bioinformatics) protein data bank.
- 12. Structure of Rv0554 on spdbv:
- 13. STRUCTURE RETRIVAL: Homology modeling using software modeller 3 files of different format were made of extension .atm, .ali, .py Final five models were obtained.
- 14. STRUCTURE VALIDATION: Five best models were ready . We viewed these models in SPDB viewer software to select the best model .we analyzed all models in the structure analysis and verification server. All these five models were prochecked. Upload pdb file then procheck. Pdb file with least warning selected.
- 17. LEAD IDENIFICATION: By using the software ligsite buliding pocket sites were created for the resulting molecule.
- 19. DEVELOPMENT OF LEAD TO ACTIVE SITE: Software named LIGBUILDER used for development of lead to active site. Best hex file(pocket file made by software hex) and file with extracted heat atoms . Pocket command pocket(space)pocket.index grow Process
- 20. DOCKING: The basic assumption underlying in-silico(SBDD) based Drug designing is that a good ligand molecule bind tightly to its target. Hence ,these ligand molecules are analyzed for their binding affinity . The molecule having maximum negative value of free energy and minimum root mean square value is selected. This will be done by a software AUTODOCK.
- 22. Ligand before and after docking
- 23. 3-D structure in SPDB viewer
- 25. PROPOSAL FOR FINAL MOLECULE: PASS(Prediction of activity spectra for substance), this online tool predict over 3500 kinds of biological activity including pharmacological effect, mechanism of action , toxic and adverse effects, interaction with metabolic enzymes and transporters , influence on gene expression etc. Ligand possesses all the properties predicted by Lipinski’s rule of five and ability to solublised in the body & the drug likeness is 0.31 , which indicates , it is very much similar to know drug , hence supporting it to be as prospective drug.
- 26. BIBLOGRAPHY: SITE ACCESSED *RCSB PDB-www.pdb.org/ *LIGSITEcsc – projects.biotec.tu-dresden.de/pocket/ *NCBI www.ncbi.nlm.nih.gov/ *PubMed.home-NCBI www.ncbi.nlm.nih.gov>NCBI>literature *SAVes-NIH MBI Laboratory for Structural Genomics And Proteomics *nihserver.mbi.ucla.edu/SAVES/Server
- 27. SOTWARES USED: *Modellar9v8 *Procheck *Ligsite *Auto dock tools 1.5.4 *Python 2.5 *Ligbuilderv1.2 *Hex6.3 *Spdb-viewer *Marvin-sketch *OpenBabel GUI *Mol Inspiration *Molsoft LLC *PASS (Prediction of Activity Spectra for Substances)