DEENBANDHU CHHOTU RAM UNIVERSITY OF SCIENCE AND TECHNOLOGY

MURTHAL (SONIPAT)

TRAINING AT
INDIAN BIOLOGICAL SCIENCES AND RESEARCH INSTITUTE
Noida , Uttar Pradesh , 201301
Submitted by:
Neha Chaursiya
20001008009
7th Sem
B.Tech(BIOTECHNOLOGY)
 SUMMER TRAINING
ON
“IN SILICO DRUG DESIGNING FOR BREAST CANCER”

INDIAN BIOLOGICAL SCIENCES AND RESEARCH INSTITUTE

UNDER THE GUIDANCE OF 4 WEEKS TRAINING
Resp. Mr. Gaurav Madan (29 July 2022 – 7 Sept. 2022)
(Director)
Resp. Mr. Bharat Madan
(Director)
 What Is Breast Cancer
• Breast cancer is a malignant tumor that
starts in the cells of the breast.

• A malignant tumor is a group of cancer

cells that can grow into (invade)
surrounding tissues or spread
(metastasize) to distant areas of the
body.

• The disease occurs almost entirely in

women, but men can get it, too.
 What Is Breast Cancer
• Most commonly from the inner lining
of milk ducts or the lobules that
supply the ducts with milk.

• Cancers originating from ducts are

known as ductal carcinomas, while
those originating from lobules are
known as lobular carcinomas.
 Types of Breast Cancer
There are many types of breast cancer

1. Ductal carcinoma in citu (DCIS)

2. Invasive Ductal Carcinoma.

3. Inflammatory Breast Cancer

4. Metastatic Breast Cancer

5. Some other specific types

 1. Ductal carcinoma in citu (DCIS)
It is a non-invasive cancer where abnormal
cells have been found in the lining of the
breast milk duct.

The atypical cells have not spread outside of

the ducts into the surrounding breast tissue.

Ductal carcinoma In situ is very early cancer

that is highly treatable, but if it's left untreated
or undetected, it can spread into the
surrounding breast tissue.
 2. INVASIVE DUCTAL CARCINOMA:
The abnormal cancer cells that began
forming in the milk ducts have spread
beyond the ducts into other parts of the
breast tissue.

• IDC is the most common type of breast

cancer, making up nearly 70- 80% of all
breast cancer diagnoses.

• IDC is also the type of breast cancer that

can most commonly affects men
 3. Inflammatory Breast Cancer
Inflammatory Breast Cancer is an an aggressive and fast growing
breast cancer in which cancer cells infiltrate the skin and lymph
vessels of the breast.

It often produces no distinct tumor or lump that can be felt and

isolated within the breast.

But when the lymph vessels become blocked by the breast cancer
cells, symptoms begin to appear.
 4. Metastatic Breast Cancer:

The cancer has spread to other parts

of the body.

This usually includes the lungs, liver,

bones or brain.
 Risk Factors
There are some risk factors for the breast cancer:

1. Gender.

2. Age.

3. Genetics related and Family history.

4. Alcohol and tobacco

5. Personal history of breast cancer.

6. Menstrual periods.

7. Having children.

8. Birth control.

9. Hormone replacement therapy

1. Gender

Women are much more likely to develop breast cancer

than men.

2. Age

The chance of getting breast cancer

goes up as a woman gets older.

About 2 of 3 women with invasive breast

cancer are 55 or older when the cancer
is found.
 3. Genetics related and Family history.

If one have parents, siblings, children or other

close relatives who’ve been diagnosed with
breast cancer, they are more likely to develop
the disease at some point in of life. About 5% to
10% of breast cancers are due to single
abnormal genes that are passed down from
parents to children, and that can be discovered
by genetic testing.
• The most common changes are those of the
BRCA1 and BRCA2 genes. Women with
these gene changes have up to an 80%
chance of getting breast cancer during their
lifetimes
 4. Alcohol and tobacco

•Tobacco: Use of tobacco is linked to many different types of cancer,

including breast cancer.

•Alcohol: Drinking alcoholic beverages increases the risk of breast

cancer, even among very light drinkers (women drinking less than half
of one alcoholic drink per day). The risk is highest among heavy
drinkers. Globally, about one in 10 cases of breast cancer is caused by
women drinking alcoholic beverages. Drinking alcoholic beverages is
among the most common modifiable risk factors.
 5. Personal history of breast cancer.

A woman with cancer in one breast has a

greater chance of getting a new cancer in
the other breast or in another part of the
same breast.

This is different from a return of the first

cancer (called a recurrence).
6. Menstrual periods.

• Women who began having periods early

(before age 12) or who went through the
change of life (menopause) after the age
of 55 have a slightly increased risk of
breast cancer.

• The increase in risk may be due to a

longer lifetime exposure to the hormones
estrogen and progesterone
7. Having children

• Women who have had no children or

who had their first child after age 30 have
a slightly higher breast cancer risk.

• Having many pregnancies and becoming

pregnant at a young age reduce breast
cancer risk.
8. Birth control.

• Studies have found that women using oral

contraceptives (birth control pills) have a slightly
greater risk of breast cancer than women who
have never used them.

9. Hormone replacement therapy

• People who use hormone replacement therapy (HRT) have a higher

risk of being diagnosed with breast cancer
 SYMPTOMS
Possible signs of breast cancer include:
•A change in the size, shape or contour of your breast.
•A mass or lump, which may feel as small as a pea.
•A lump or thickening in or near your breast or in your
underarm that persists through your menstrual
cycle.
•A change in the look or feel of your skin on your
breast or nipple (dimpled, puckered, scaly or
inflamed).
•Redness of your skin on your breast or nipple.
•An area that’s distinctly different from any other area
on either breast.
•A marble-like hardened area under your skin.
•A blood-stained or clear fluid discharge from your
nipple.
 DIAGNOSIS

• Breast exam
• Mammograms
• Breast ultrasound
• Imaging tests
Breast MRI scan
• Biopsy

BREAST EXAM
 Clinical Breast Exam(CBE)
 Breast - Self Exam (BSE)
 PHOSPHOINOSITIDE 3-KINASE
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol
3-kinases, are a family of enzymes involved in cellular functions such
as cell growth, proliferation, differentiation, motility, survival and
intracellular trafficking, which in turn are involved in cancer.
The phosphatidylinositol 3-kinase (PI3K) pathway is one of the
major pathways in oncogenesis, and PI3K alterations are
common in all breast cancer subtypes. Despite modest clinical
activity and a high toxicity rate, pan-PI3K inhibitors paved the way
for selective PI3K inhibitor development.
 MATERIAL AND METHOD

MATERIALS:
•KEGG PATHWAY DATABASE
•GOOGLE SCHOLAR
•PUBCHEM
•MARVIN SKETCH
•MOLINSPIRATION
•SNIPPING TOOL
•MOLEGRO VIRTUAL DOCKER
 KEGG PATHWAY DATABASE
KEGG (Kyoto Encyclopedia of Genes and Genomes) is a collection of
databases dealing with genomes, biological pathways, diseases, drugs, and
chemical substances. KEGG is utilized for bioinformatics research and
education, including data analysis in genomics, metagenomics, metabolomics
and other omics studies, modeling and simulation in systems biology, and
translational research in drug development.

GOOGLE SCHOLAR:
Google Scholar provides a simple way to broadly search for scholarly literatur
e. From one place, you can search across many disciplines and sources: arti
cles, theses, books, abstracts and court opinions, from academic publishers,
professional societies, online repositories, universities and other web sites.
 PUBCHEM:
PubChem is a database of chemical molecules and their activities against
biological assays. The system is maintained by the
National Center for Biotechnology Information (NCBI), a component of the
National Library of Medicine, which is part of the United States
National Institutes of Health (NIH). PubChem can be accessed for free through
a web user interface.PubChem contains multiple substance descriptions and
small molecules with fewer than 100 atoms and 1,000 bonds.

MARVIN SKETCH:
MarvinSketch is a Java based chemical drawing tool. MarvinSketch allows you to
create and edit molecules in various file formats including MDL mol, Compressed
mol, unique SMILES, SMARTS, Sybyl mol, PDB, CML, XYZ, POV-Ray.
It has a rich list of editing featurs, is chemically aware and is able to call chemAxon
structure based calculation plugins for structure on the canvas.
MOLINSPIRATION CHEMINFORMAATICS :
Molinspiration offers broad range of cheminformatics
software tools supporting molecule manipulation and processing, including SMILES
and
SDfile conversion, normalization of molecules, generation of tautomers
, molecule fragmentation, calculation of various molecular properties needed in QSA
R, molecular
modelling
and drug design, high quality molecule depiction, molecular database tools supporti
ng substructure search or similarity and
pharmacophore similarity search.
MOLEGRO VIRTUAL DOCKER:
Molinspiration is written in java , therefore can be used used
Molegro virtual docker
on any computer is a protein-ligand
platform.
docking simulation program that allow us to carry out docking simulation in a fully i
ntegrated computational package.
Molegro Virtual Docker
handles all aspects of the docking process from preparation of the molecules to d
etermination of the potential binding sites of the target protein, and prediction of th
 METHODS
KEGG PATHWAY
•Open the website https://www.genome.jp/kegg/pathway.html .
•Click on the Human diseases option .Now select the desired human disease we
want to work on ( biz. Breast Cancer ).
•Now we can see the whole pathway involving the genes responsible of the breast
cancer (highlighted in red color ).
•Select a gene responsible for the disease from the kegg pathway ( highlighted in
red color , biz P13K ).
• Now scroll down to Structure and download the PDB format file which contains a
lot of protein structures.
•After downloading the PDB format now download the respective Drug Target
Database from the Pubchem option in SDF format.
MARVIN SKETCH:
• Click on the start button in PC then type for marvin sketch and open it.
• Copy the downloaded drug target and paste it on marvin sketch for reference to
calculate the molecular properties of drug by the help of molinspirantion.
MOLINSPIRATION CHEMINFORMATICS:
•Open Molinspiration Cheminformatics fron the Google and draw the structures of
drugs by the help of marvin sketch. Then click on the calculation if molecular
properties and prediction of bioactivity.
•It is done to check if the drug target is following the Lipinski rule of 5 or not.
•If the calculated properties show normal range ( no highlighted numbers) that
means the drug target is good to make a ligand . If not ( as the calculated
properties shows numerical in highlighted color ) then we need to fix the respective
drug target by removing molecular weight of Nitrogen and oxygen atoms. Once
they are done they are copied by Control + C keyword and paste on Marvin sketch
software(PDB format).
MOLEGRO VIRTUAL DOCKER:
•With the help of this software we can do analysis of complex when a ligand and a Protein
are bound to each other to form a stable complex. Simply open the software then click on the
open file option . Now open the respective protein structure and then open the respective
ligand . Click on the Prepare molecules and remove Water. Then click on the Detect Cavities
option where the maximum numbers of cavities are 3.
•Open Docking Wizard and enable the Energy Thresh hold option .wait for the whole process
to be completed . when the results appear on the screen drag the results ( red colored file) to
the screen . Now click on create surface option.
•Take screenshots of the panel with
•the following criteria –
•Only Surface
•Only cavities
•Only Poses
•Cavity and Poses
•Poses and Proteins
•And save all the respective screenshots in their files .
LIGAND1-
DOCKING
 LIGAND -1 LIGAND -2

S.NO. PROTEIN MOLDOCK H BOND MOLDOCK H BOND

SCORE SCORE
1 5UBT -93.2719 -4.33062 -79.2915 0

2 6G6W 95.6517 -1.01486 -115.7595 -3.1429

3 6OCO 20.7157 -4.02917 6.95912 -3.34051

4 6PYV 2000.86 1.61335 -87.25 -4.34037

5 7JIS 103.277 -6.04969 131.639 -4.99009

 LIGAND - 3 LIGAND -4

S.NO PROTEIN MOLDOCK H BOND MOLDOCK H BOND

SCORE SCORE
1 5UBT -118.456 -2.6656 -117.348 -2.74537

2 6G6W -122.374 -5.77837 -125.466 -2.35258

3 6OCO 20.5425 -8.82118 -84.3583 -10.442

4 6PYV -123.093 -4.1004 -123.123 -3.76503

5 7JIS -124.162 -4.05346 -117.011 -2.5

 LIGAND -5 LIGAND-6

S.NO PROTEIN MOLDOCK H BOND MOLDOCK H BOND

SCORE SCORE
1 5UBT -51.4352 0.801211 -79.2915 0

2 6G6W 65.8106 -0.235455 81.5231 -3.65764

3 6OCO -30.6797 3.87352 -44.0653 -7.19392

4 6PYV -93.4851 -2.09919 0.761148 -4.58038

5 7JIS 2127.05 1.26803 103.861 0

LIGAND OF PROTEIN MOLDOCK VALUE H BOND

LIGAND- 2 -115.7595 -3.1429

LIGAND- 4 -125.466 -2.35258

LIGAND -5 -93.4851 -2.09919

 CONCLUSION
Ligand 4 has the minimum energy when docked with which is -2.35258 the Ligand 4 when docked with
6G6W Protein produce -3.1429 with 6G6W the minimum energy produced is 22.45 by market drug when
docked with 5 BUG protein .
Therefore Ligand 2 ,4 and 5 are the better drug treatment for Breast Cancer disease because it has got
minimum energy and will have more stable when interaction with protein will occur .
Targeted drug therapy uses medicines that are directed at (target) proteins on breast cancer cells that help
them grow, spread, and live longer. Targeted drugs work to destroy cancer cells or slow down their growth.
In about 15% to 20% of breast cancers, the cancer cells make too much of a growth-promoting protein
known as HER2. These cancers, known as HER2-positive breast cancers, tend to grow and spread more
aggressively than HER2-negative breast cancers. Different types of drugs have been developed that target
the HER2 protein. Any of these drugs can be given along with an aromatase inhibitor (AI) or fulvestrant to
women with advanced breast cancer who have gone through menopause. Any of these drugs can be given
with fulvestrant or an aromatase inhibitor to women with advanced breast cancer who are still having
regular periods (premenopausal) or are almost in menopause (perimenopausal). These women, however,
must also be on medicines, such as luteinizing hormone-releasing hormone (LHRH) analogs, that stop the
ovaries from making estrogen or have their ovaries removed with surgery.