IN-SILICO DRUG

DESIGNING

Various sectors of IBI:

CONTENTS:
Drug designing
Tuberculosis - an overview
Target Identification
Target Validation
Structure Retrieval
Structure Validation
Final Model
Active Site Identification
Lead Identification

Lead Insertion In Active Site

Development Of Lead In Active Site
Docking
Proposal to Final Molecule
Bibliography

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.

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.

Chest X-ray:infetion in
lungs

Symptoms of active TB:

Chronic cough
Fever
Night Sweats
Blood-tinged sputum
Unusual weight loss

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

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(subheading) 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.

BLAST against homo-sapiens

Structure of Rv0554 on
spdbv:

STRUCTURE RETRIVAL:

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.

FINAL MODEL/STRUCTURE VALIDATION:

LEAD IDENIFICATION:
By using the software ligsite buliding

pocket sites were created for the

resulting molecule.

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

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.

Ligand before and after

docking

3-D structure in SPDB viewer

BIOSAFETY:MOLSOFT LLC

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
Lipinskis 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.

BIBLOGRAPHY:
SITE ACCESSED

*RCSB PDB-www.pdb.org/
*LIGSITEcsc projects.biotec.tudresden.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

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)

THANK YOU