BIOINFORMATICS

SUBMITTED BY:
PALLAVI GUPTA [MCA/10042/19]
 CHEMOINFORMATI
CSIN DRUG DEVELOPMENT
AND ITS APPLICATION
 HISTORY OF CHEMOINFORMATICS DRUG DISCOVERY AND DEVELOPMENT
WHAT IS CHEMOINFORMATICS?

MAJOR ASPECTS OF CHEMOINFORMATICS PROCESS OF DRUG DEVELOPMENT

COMMON CHEMINFORMATICS PATTERN TOOLS USED FOR DRUG DEVELOPMENT

Contents
APPLICATIONS OF CHEMOINFORMATICS APPLICATIONS OF DRUG DISCOVERY IN
CHALLENGES TO CHEMOINFORMATICS MODERN ERA

CHEMINFORMATICS AND OTHER DISCIPLINES CONCLUSION

FUTURE TRENDS OF CHEMINFOMATICS
 HISTORY OF Cheminformatics is the mixing of those
information resources to transform data into
information and information into knowledge for
CHEMOINFORMATICS the intended purpose of making better
decisions faster in the area of drug lead
identification and optimization.

The term cheminformatics was defined in its

application to drug discover, for instance, by
F.K. Brown in 1998
Cheminformatics combines the scientific
working fields of chemistry, computer science,
and information science—for example in the
areas of topology, chemical graph
theory, information retrieval and data mining in
the chemical space. Cheminformatics can also
be applied to data analysis for various
industries like paper and pulp, dyes and such
allied industries.
 WHAT IS CHEMOINFORMATICS ?
To handle large amount of information

To move chemistry into the computer age

Cheminformatics (also known
as cheminformatics and chemic
al informatics) is the study .
of large amounts of chemical To move from data to knowledge
information. It is done mostly
with the help of computers. WHY DO WE NEED
These tools are used CHEMOINFORMATICS
by pharmaceutical companies
to discovery new drugs.
? To get funding
Cheminformatics
encompasses the design ,
creation , organization
,management , retrieval , Data information knowledge
analysis , dissemination ,
visualization , and use of
chemical information.
Measurements/Calculations
MAJOR ASPECTS OF
CHEMOINFORMATICS
Information Acquisition is a process of generating Databases: Development of databases
and collecting data empirically or from theory 01 04 for storage and retrieval of small
(molecular simulation) molecule structures and their properties.

Information use which includes Data Analysis, Machine learning: Training of decision trees,
correlation, and application to problems in the 02 05 neural networks, self organizing maps, etc.
chemical and biochemical sciences. on molecular data.

Information management deals with Predictions: Molecular properties relevant to drugs,

03 06 virtual screening of chemical libraries, system
storage and retrieval of information.
chemical biology networks.
COMMON CHEMINFORMATICS PATTERNS
Markush This is a topological pattern
structure or used by chemists for many
generic years. It is determined by
structure experience. It is an efficient
way to represent an
unlimited number of
compounds with the same
scaffold. Additional
restrictions can be applied to
make the pattern more
specific. It is suitable for lead
optimization and hit-to-lead
efforts.

Fingerprint This is the topological pattern

systematically generated
from an algorithm. This
pattern has no human bias,
but can be meaningless to
chemistry. It is used in HTS
data mining.

Three- This patt ern is derived,

dimensional manually or computationally,
pharmacophore from a three-dimensional
molecular model. The
pattern is based upon a
physical model and binding
mechanism. It is sensitive to
conformation changes.
Better results are obtained
when supported by crystal or
NMR structural data. It is
suitable for lead
optimization.
Regression Regression methods are the most
traditional approaches for pattern
recognition. These methods assume
the variables are continuous and
the curve shapes are pre-defined.
For multidimensional data, curve
patterns are not known and trying
all possible curves is very time
consuming. In these cases, genetic
algorithms may be applied to
partially solve the problem of
identifying curve patterns.

Decision tree This approach is applied when there

classification are a great number of descriptors
and, the descriptors have various
value types and ranges.

Hierarchical This approach assumes the objects

clustering have hierarchical characters. The
methods require similarity or
distance matrices. The approach
may produce multiple answers for
users to explain or with which to
experiment.

Non- The approach assumes the objects

hierarchical have non-hierarchical characters,
clustering and the number of clusters is
known prior the computation. The
method requires similarity or
distance matrices. The approach
may produce multiple answers for
users to explain or with which to
experiment.
APPLICATIONS OF CHEMOINFORMATICS

STORAGE AND RETRIEVAL : VIRTUAL SCREENING :

helps in storage , indexing & identification of novel active
search of information. molecules in large compound
databases.

VIRTUAL LIBRARIES : QUANTITATIVE STRUCTURE

chemical data can pertain to ACTIVITY RELATIONSHIP :
real or virtual molecules. predict activities of compounds
from their structure.

FILE FORMATS : uses

formats like SDF:2D &
3D, Mol:2D,
Mol2:3D,Xml
Three Fundamental Questions
of A Chemist:
The fundamental and
lasting objective of synthesis is
not production of new
compounds but production of
properties.
If this is accepted,
chemists have to face three
fundamental questions.
a. Which compound will
have the desired property?
b. How can I make this
compound?
c. Did I make this
compound (what is the product
of my reaction)?
Toxicity Prediction and Risk
Assessment:
Society has become increasingly
interested and concerned about the
impact of chemicals on the
environment and on human health.
Therefore, chemicals should be
introduced into the market or used
only if they have been proven to be
safe.
Furthermore, the impact of
chemicals on the environment is of
much concern in society. Models for
persistence, bioaccumulation and
toxicity of chemicals in all kinds of
organisms are asked for.
CHALLENGES
TO
CHEMOINFORMATICS
Modeling Biological Systems:
The next step is then a focus on unraveling the
events in living organisms. It should be realized that
life is maintained by (bio)chemical reactions;
modeling and understanding them is essential for
getting deeper insights into the events that keep living
species alive. This could provide a basis for curing
diseases. New research fields have been conceived
of, with names such as systems chemistry, systems
biology and systems chemical biology. Whatever the
names, the aim is to further an understanding of
biological systems even to a point that they can be
altered. A collaboration between cheminformatics and
bioinformatics is essential for this purpose.
The newest developments aim at modeling entire
human organs. Large-scale government-supported
projects in the U.S. and in Germany have been
initiated to develop models for the human liver, the
virtual liver v-Liver at EPA [ and the German virtual
liver project networks
CHEMOINFORMATICS AND OTHER DISCIPLINES
Cheminformatics and Machine learning although
machine learning is widely used for structure property
modelling, cheminformatics can be considered as a
very specific area of its application. The specificity of
cheminformatics results from (i) the nature of chemical
objects, (ii) the complexity of the chemical universe and
(iii) a possibility to take into account an extra-
knowledge. The basic chemical object is a graph (or
hyper graph), rather than simple fixed-sized vector of
numbers as in the typical applications in mathematical
statistics and machine learning. This dictates the need
to apply graph theory, to develop novel descriptors and
structured graph kernels, and to apply machine learning
methods capable of dealing with structured discrete
data.
Finally, one can use the relationships
between different properties issued
from physicochemical theory. (For
example, the Arrhenius law could be
particularly useful upon the modelling
the rate constants). These relationships
could be integrated into
cheminformatics workflow as an external
knowledge.
The second important distinction comes from the
fact that the chemical data result from an
explorative process in a huge chemical space rather
than from specially organized sampling. Hence,
they cannot be considered as representative,
independent and identically distributed sampling
from a well defined distribution. Thus, special
approaches are Cheminformatics as a Theoretical
Chemistry Discipline needed to treat this
problem: various strategies to explore chemical
space, the “applicability domain” concept, the active
learning approach, etc.
Cheminformatics and Bioinformatics
Unlike cheminformatics dealing with “chemical size”
molecules, bioinformatics uses computational tools to study
the structure and function of biomolecules (proteins, nucleic
acids). This is a broad field mostly involving 3D (force field
and quantum mechanics calculations) and 1D (sequence
alignment) modeling. In the latter, a biomolecule is
represented as a string of characters (building blocks).
Graph and fixed size vector models used in
cheminformatics are very rarely used in bioinformatics. In
this sense, chemo and bioinformatics are “complementary”.
 FUTURE TRENDS OF CHEMINFORMATICS
1. Global databases, integration of multiple data
sources, public (Wikipedia-like) curation.
2. Use of Computer Assisted Structure
Elucidation (CASE) process and Computer
Assisted Synthesis Design (CASD) would be
integrated into the daily work process of bench
chemists.
3. Cheminformatics methods will be extended to
theoretical chemistry, stimulation of reaction;
study of proteins will be the future areas of
thrust for cheminformatics.
4. Use of large chemo genomics databases
(WOMBAT, GVK …)
5. Text and image mining, automatic extraction of
useful information from publications and patents.
6. Integration with bioinformatics, with focus on
ligand protein interactions and pharmacophores
7. Disappearing border between cheminformatics
and computational chemistry
8. In technology area –modularization, web
services
9.Open source collaborative software development
10. Using all the advanced cheminformatics
system, it enhances the drug discovery rapidly and
with low cost and helps to eminent scientists to
synthesize the chemical molecules which lead to
helps the society.
DRUG
DEVELOPMEN
T
DRUG DISCOVERY AND
DEVELOPMENT
Drug is an active chemical substance used for diagnosis, mitigation,
treatment and prevention(DMTP) of diseases of humans and animals.

Also includes chemical substances, diagnostic, abortive and

contraceptive substances.

Drug discovery is the process of identifying new medicines.

It involves a wide range of biological, chemical and

pharmacological disciplines.

Drug discovery take years to decade for discovering a new drug

and very costly.
PROCESS OF DRUG DISCOVERY
TOOLS USED FOR
DRUG
DEVELOPMENT
The development of software and tools for computer assisted
organic synthesis are under vast development. This has
resulted in many tools and representations for chemical
structures. Some of the tools are listed below :
Chemdraw
Chemwindow Some other tools such as, CAS Draw, DIVA (Diverse
Chemreader Information, Visualization and Analysis), Structure
Checker Accord, DS Accord Chemistry Cartridge,
Chemsketch
MarvinSketch PowerMV, TINKER, APBS, ArgusLab,
logchem Babel, ioSolveIT, ChemTK, Chimera, CLIFF, Dragon,
wendi gOpenMol, Grace, JOELib, Jmol, IA_LOGP, Lammps,
chemmine MIPSIM, Mol2Mol, AMSOL, MOLCAS, Molexel, ICM-
pubchem Pro, ORTEP, Packmol, Polar, XLOGP,PREMIER
open babel Biosoft, Q-chem, ALOGPS, Qmol, SageMD, ChemTK
Lite, Transient, CLOGP,TURBOMOLE, UNIVIS, VMD,
WHATIF, GCluto, COSMOlogic, KOWWIN are also
used.
APPLICATIONS OF DRUG DISCOVERY IN MODERN ERA

1 2 3 4 5
Jun-Ru Wang and coauthors
studied a new series of ester
Feng Xu and coauthors derivatives of 10-hydroxycanthin-6-
employed the 3D culture of Rizk E. Khidre and one using a simple and effective
MCF-7 and SMMC-7721 colleagues designed synthetic route as part of their
Drugs function by Developers designed and synthesized a continuing research on canthin-6-
cells based on the hanging
interacting with and synthesized a novel series of one antimicrobial agents. They
drop method and evaluated
multiple protein series of nine quinoline characterized the structure and
the anti-proliferative activity
targets to create a enmein-type ent- compounds and antimicrobial activity of each
and cellular uptake of two
molecular interaction kaurane diterpenoid screened for their compound, investigated the
promising anti-tumor drug
signature that can be and furoxan-based antimalarial structure-activity relationship, and
candidates, evodiamine
exploited for rapid nitric oxide (NO) activities, with the identified the promising lead
(EVO) and rutaecarpine
therapeutic donor hybrids from hope that these compound that had significant
(RUT), in 3D multicellular
repurposing and commercially compounds could antimicrobial activity against all the
spheroids and compared the
discovery. available oridonin. lead to the fungi and bacterial strains tested for
results with those obtained
from 2D monolayers availability of better the development of novel canthine-
drugs to treat 6-one antimicrobial agents.
malaria.
CONCLUSI Cheminformatics can hence be described as the application of
informatics methods to solve chemical problems. It has developed
over the last 40 years to a mature discipline that has applications in
ON many areas of chemistry. It is an important scientific discipline that
stands on the interface between chemistry, biology and Information
Technology. Cheminformatics spans a very broad range of
problems and approaches which are often inter-related and
sometimes difficult to categorize. As high throughput technologies
and combinatorial chemistry continue to advance, informatics
techniques will become indispensable in managing and analyzing
the exploding volumes of data. By organizing, the data,
Cheminformatics will further introduce advancements in chemistry
and open new possibilities in the field of drug discovery. There are
still many problems that await a solution and therefore many new
developments in cheminformatics are foreseen. We believe that
this review will be the defining theme and might help to provide
much new advancement in the field of cheminformatics in coming
years. Hopefully, the availability of information related to
cheminformatics will catalyze further advancements and would
open new advancements in this field.
Thank You