Study of Anticancer Compound by Docking.

1. IDENTIFICATION OF NOVELANTICANCER COMPOUND
AGAINST ZINC FINGER PROTEIN (BTB): DOCKING STUDIES
Undertaken Supervision of
Sanjay Kumar
Programmer, Bioinformatics Center, Biotech Park, Lucknow
Presented by:
Mudit Kumar Srivastava
M.Sc Bioinformatics
Roll no:9Central University Of South Bihar 1

2.  Cancer is a group of diseases characterized by the uncontrolled growth and spread
of abnormal cells.
 Generally cancer cells develop from normal cells due to damage of DNA. DNA
damaged might be inherited from the parents, which accounts for inherited cancers
Or by certain environmental exposures such as Smoke, chemical radiation,
infection, obesity, and also from tobacco.
 From the literature review Cancer is the leading cause of death in the world,Half of
men and one third of women in the United States will develop cancer during their
lifetime.
Types of cancer:
There are more than 120 types of cancer some are most recently viewed:
Bladder cancer Liver cancer Leukemia cancer
Brain cancer Lung cancer Thyroid cancer
Breast cancer Prostrate cancer Ovarian cancer
Cervical cancer Oral cancer Pancreatic cancer
Kidney cancer Skin cancer Uterine cancer
CANCER: A BIG PROBLEM
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3. Central University Of South Bihar 3

4. Central University Of South Bihar 4

5. Aimed to determine the activity of an anti-cancerous compound
which may works as effective anti-cancer drug for the cure of
cancer diseases.
OBJECTIVE
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6.  ZBTB7A called as Pokémon stands for "POK erythroid myeloid ontogenic factor"
is a gene that may act as a master switch for cancer and is responsible for the
proliferation of cancer through out surrounding cells.
 ZBTB7A which is a cancer causing gene, it expressed in all proliferating cells highly
in malignant tissues than in the corresponding benign or normal tissue (breast,
lung, prostate).
 Zinc finger and BTB domain-containing protein 7A is a protein that in humans is
encoded by the ZBTB7A and composed of 584 amino acids (a.a).
 A zinc finger is a small protein structural motif that is characterized by
the coordination of one or more zinc ions in order to stabilize the fold.
 The BTB (Born to bind) or POZ domain is a protein-protein interaction motif that
is found throughout eukaryotes.
 It belongs to the POK family of transcriptional repressors.
TARGET GENE & PROTEIN
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7.  In human it was proved that, it is an important molecular switch to an oncogenesis
but little is known about the regulation of this gene expression.
 The mechanisms of Zbtb7A gene expression regulation is of importance for
understanding the precise roles of Zbtb7A in physiological and pathological
processes.
 Zbtb7A is also a repressor of the ARF tumor suppressor gene and it expressed at
high level.
 There are only 21 articles specifically referring this gene in pubmed which is very
less.
 So, Functionally this gene has been tested and reported as a association to a disease
of cancer (Breast,lung,Prostrate).
WHY ZBTB7A?
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8. Protein:
PDB ID: 2NN2 Organism: Homo sapiens Length: 584 a.a
Molecule: Zinc finger and BTB domain-containing protein 7A
Gene name: ZBTB7A Chain: A,B
Ligand Search:
 Total 80 anti cancer compounds that have anti cancerous properties, were retrieved
from literature and there 3D structure and other properties were downloaded from a
from the Pubchem database.
MATERIALS
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9. Databases:
Uniprot www.uniprot.org
Ncbi www.ncbi.nlm.nih.gov
Pdb www.rcsb.org
Pubchem https://pubchem.ncbi.nlm.nih.gov
Tools and Software's:
Openbabel v2.3.1
AutoDock v4.2
Cygwin Terminal
Chimera v1.10.1
PyMol v0.99
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10. METHOD AS A FLOW CHART
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11. Target Receptor
 The BTB domain sequences of Zinc finger protein were downloaded from the
uniprot database for the blast to find the structure.
 The blast result of the domain shows the 100% query and identity with the (Pdb id:
2NN2), so there was no needed to model the structure and hence it uses as the target
receptor for Docking.
Blast result of target protein
.
RESULT & DISCUSSION
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12. Ligand
 By applying Lipinski rule of five we get only 54 compounds out of 80 for docking.
 From the 54 Docked compounds the top ten compounds, having minimum binding
energy were selected.

Table: Top ten Docked compounds
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13. Interaction Result
 By adding the atom of the ligand from .dlg file into the protein .pdb file the
interacted ligand binding site can be seen.
 The interaction analysis of protein and ligand complex have been done with the
help of “LIGPLOT” which is an automatically generated schematic diagram tool of
protein-ligand PDB file.
Table: Top Ten Compounds with there Hydrogen Bonds and Hydrophobic Interaction
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14.  The top ten interacted compounds having no of hydrogen bonds and hydrophobic
interaction.
 Among these top ten compounds, those having the maximum no. of hydrogen bond
and lowest binding energy, we selected it as a best anti cancerous compound.
Fig: Target protein (2NN2) binding with the ligand view generated by Ligplot
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15. CONCLUSION
 The Zinc finger and BTB domain-containing protein7 2NN2 selected as the target
protein receptor which docked with 54 anti cancer compounds.
 The protein-ligand complex with the lowest binding energy, hydrogen bonds and
may be considered as best drug candidate and may use for the treatment of
cancerous diseases after experimental validation.
 We select Cyproterone (id 5284537) pose6, having the binding energy -5.36 and the
no. of hydrogen bond binding is 2 which are maximum among the top ten pose,
which may work as effective anti-cancer drug for the cure of cancerous diseases.
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16.  I am grateful to my guide Mr. Sanjay Kumar, Programmer, Bioinformatics Center,
Biotech Park, Lucknow, for his generous consideration and kindness toward this
Project.
 Thankful to my college Central University of South Bihar and Professors,
Bioinformatics Center to permit me the permission to work on this project .
ACKNOWLEDGMENT
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17. Central University Of South Bihar 17