An Insilico Drug Designing Approach to Target the BRCA1 Protein involved in Breast cancer

Author Name(s): *Shilpi Pal
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Breast Cancer is one of the major health threats of the decade that are troubling the mankind. Since long the studies have been conducted in treating this disease. Recent studies have revealed that the gene involved in causing this condition is BRCA, termed as Breast Cancer Associated gene. The current study involved the complete insilico analysis of this gene. Its functional study and the Structural Analysis. This is followed by identifying the potential drug candidate from PubChem database. Several screening techniques have been employed to check the feasibility and efficiency of the drug. Lipinsky rule was employed to check the drug likeliness of the compound, Toxicity and ambiguity of the chemical are screened using Dundee ProDrg Server. The final 3D chemical obtained was used to dock with the protein structure using HEX automatic docking software. The best chemical that can be used in the therapy can be selected based upon the lowest energy values of docking.


Breast Cancer, BRCA1 gene, cell-cycle progression, cell-cycle check points, transcriptional pathways, apoptosis, protein-protein interactions, phosphorylation and carcinogenesis.


Bioinformatics is a type of interdisciplinary field which has all developed method and software tools for all biological data and to understand it. Bioinformatics is a combination of many fields of subjects to study and for the processing of the biological data. Homology Modeling is also known as the comparative modeling of a protein which refers to the construction of the atomic resolution model of the target protein from the known or given amino acid sequences and an three dimensional structure of a related homologous protein. It has been shown that the structure of a protein are more conserved than the sequences of the protein of the homologous, but the sequences which falls below the 20% sequence identity can have very different structure.[1] They can produce high-quality structure models when both the target and the template are closely related which helps in the formation of a structural genomics consortium which helps in the representation of the structures for all the classes of the protein folds. RATIONAL DRUG DESIGNING is also known as the  Drug Design or the Rational Design. It is a process which helps in finding the new medication which is based on the knowledge of biological target. The small molecules design are involved which are complementary in shape and it is charge to the biological target. The traditional method of the discovery of a drug is based on the trail-and-error of the chemical substances on the cultured cells or the animals and the effects on the treatments, rational drug design begins with the hypothesis which is based on the modulation of a specific biological target which may have the therapeutic value. BREAST CANCER is a cancer which develops from the breast tissue. Signs of the Breast Cancer are lump in the breast, a change in breast shape, dimpling of the skin, fluid coming from the nipple, or a red scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodesshortness of breath, or yellow skin. The factors which develops the Breast Cancer include obesity, lack of physical exercise, drinking alcoholhormone replacement therapy during menopauseionizing radiation, early age at first menstruation, having children late or not at all, and older age.

BRCA mutation is a mutation in either of the BRCA1 and BRCA2 genes which are the tumor suppressor genes. Harmful mutations in these genes which may produce the hereditary breast-ovarian cancer syndrome in affected persons. The risk of breast cancer and the ovarian cancer is higher for women which has a high risk in BRCA1 mutation than the BRCA2 mutation. Having a high risk mutation does not confirms that it will developed any type of cancer in any one’s body or any type of cancer implies that  it is caused due to the mutations , rather it can be caused due to some other factor. BRCA1 are the human genes and it has a protein product respectively. It is responsible for the repairing of the DNA. The cross linking of the DNA are the important source of the chromosomal or the DNA damage. ROLE OF BRCA1 GENE:  It provides a instructions to make a protein which acts a tumor suppressor. Tumor suppressor proteins helps in preventing the cells from growing and in the too fast division of the cells or in the uncontrolled manner.In the nucleus of a normal cells, the BRCA1 protein interacts with some other prote in for the breaks of the DNA. These breaks are caused due to natural and medical radiation or any other environmental exposures, and they also occur at the time of genetic exchange of a chromosome in the preparation of the cell division. It plays a crucial role in maintaining the stability of the genetic information of a cell.BRCA1 protein helps in the regulation of the genes and plays a important role in embryonic development.


It is quite long since Breast cancer is threatening a lives of millions of women in the globe. Researchers were able to identify the major causative protein BRCA1 that can be targeted to control the rate of cell division in the victims. The current work aimed to do the same. The work involves identification of a suitable chemical and its perfect screening so as to use if for docking with the BRCA1 receptor. The selected chemical was Dibromdulcitol, whose properties are mentioned above. The compound has been used to dock with the 3D structure of 4JLU a structure representative for BRCA1. The docking was performed using HEX 8.0 software. The docking results revealed that the above pair has the docking energy of -180.79. This indicates a perfect docking couple. Thus this compound can be used as a better drug in targeting the BRCA1 protein as a means to control cell division.

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