IDENTIFICATION OF NOVEL ANTICANCER COMPOUND AGAINST ZINC FINGER PROTEIN (BTB): DOCKING STUDIES

Undertaken Supervision ofSanjay Kumar

Programmer, Bioinformatics Center, Biotech Park, Lucknow

Presented by:Mudit Kumar SrivastavaM.Sc Bioinformatics Roll no:9Central University Of South Bihar 1

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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Cancer: A Silent

Killer

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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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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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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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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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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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METHOD AS A FLOW CHART

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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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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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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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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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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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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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