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.

1. Vikas Sinhmar
2K9/BT/8028

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.

11. BLAST against homo-sapiens

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.

16. FINAL MODEL/STRUCTURE VALIDATION:

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

24. BIOSAFETY:MOLSOFT LLC

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)