INTRODUCTION TO CHEMINFORMATICS

AND DRUG DESIGN

 Basic of cheminformatics
What is cheminformatics?
The most accepted definitions of Cheminformatics are…
• 1. “Cheminformatics is the combinationation of
chemical synthesis , biological screening and
• data mining approaches used to guide drug discovery
and development.”

• “C I is the use of computer software to assist in the

acquisition , analysis and management of data and
information relating to chemical compounds and their
properties.”
Like bioinformatics, CI is still being defined. In BI computers
are used to store, retrieve and assist in understanding
biological information, CI is the organization of chemical data
in a logical form to facilitate the process of understanding
and making inferences. Instead of a text-based retrieval
system, CI uses chemical structure that researchers provide
as input to identify similar compounds that might be
screened for biological activity.

BI deals with large molecules such as proteins and CI deals

with small molecules that are sythesized in chemical
processes says Phil Mchale vice president for product
marketing at MDL Information System.
 History of chemical information science
Chemical information has been collected and indexed for more
than 100 years now, for most of the time in the form of books and
journals.
The printed materials (costly and time consuming) .
Books also go missing and journals spend time at the binders
Since people are at the mercy of whatever index is available
and searching in time consuming
Photocopy of the printed page – word processors (or)
computer program
Chemistry material started appearing “on-line” form 1982
In 1995, the world wide web started emerging
 History of Chemoinformatics
• Historically, the field of chemoinformatics goes back
to the 1960s although the name chemoinformatics
was coined only in 1998.
• Chemical information formed an important
component of chemoinformatics. This was one of the
reasons why the Journal of Chemical Documentation
changed its name to Journal of Chemical Information
and Computer Sciences in 1975.
• Then, in turn, this journal changed its name to Journal
of Chemical Information and Modeling in 2005.
 Definitions of Chemoinformatics
• The use of information technology management has
become a critical part of the drug discovery process”

• Chemoinformatics is the mixing of those information

resources to transform data into information and
information into knowledge for the intended purpose
of making better decisions faster in the area of lead
identification and organist ion ” F.K Brown (1998)
• (It deals with the mixing of IT and management to
tranform data….)
• The Journal of Cheminformatics has just
started to appear in 2009. When the name
chemoinformatics was introduced, the term
chemometrics had already been coined.
Chemometrics did not refer to all computer
applications in the field of chemistry. Instead, it
focused on some computer applications in
analytical chemistry. This was probably the first
field of computer applications in chemistry
organized by a common name. Chemometrics
started to deal with objectives less complex
than those targeted by chemoinformatics
 Evolution of Cheminformatics

Chemical Information ( 18th century-1960)

Chemoinformatics (1961-2000)

Cheminformatics (2000-prsent)
 Contn…
• All these terms basically mean the same thing and the
use of information technology and management for
the process of drug discovery.

Chemical information employs chemical structures, data

storage and computational methods .

e.g compound registration databases , on-line chemical

literature, SAR analysis (structure activity relationship)
and molecule- property calculation.
 Chemical Information System(CIS)
• The main purpose of this is to identify a chemical
substance, find compounds similar to the target
compounds and demine the location of the
compound, and it is an inventory system.
• Chemical similarity searching databases by
chemical similarities is among the oldest and most
useful techniques in molecular modeling as
practiced by the pharmaceutical industry. It works
because it is generally true that molecules with
similar structure have similar biological activities
 Chemical Information System(CIS)…

The chemical information systems and services have

been established for many years

(i) Justus Liebig in 1832 founded Annalender pharmacie

(ii) Chemical abstarct was started in 1907

(iii) First compuetr-based system was established over

40 years ago
 Milestones in Cheminformatics
(i) Identification of a user-defined structural
pattern in a database structure.

(ii) Use of graph -searching Algorithm.

(iii)For the storage and retrieval of 2D chemical

structure .(later, 3D also)
• The problem of a unique and unambiguous representation of
chemical structures was addressed by Morgan (1965) which
led to the construction of the Chemical Abstracts Service
databases.
• Hansch and Fujita published their seminal work on
quantitatively modeling biological activity which led to the
establishment of the field of quantitative structure-activity
relationship (QSAR)
• deriving the structure of organic compounds from their mass
spectra –Application of AI to organic compound
• early 1970s, several groups at Harvard took up the problem of
computer-assisted synthesis design (CASD).
• In-house databases on chemical structures and reactions such
as MACCS, REACCs, and the Beilstein database.
• Chemoinformatics, cheminformatics, molecular informatics,
and chemical informatics are related names or even
synonyms.
• In fact, chemometrics that uses, for example, the same
techniques for analyzing data is evidently covered by
chemoinformatics.
• However, for historical reasons, chemometricians often prefer
to preserve their separate identity. For sure, however, seeing
these disciplines as a unity will help much in better
understanding the world of chemistry.
SCOPE OF CHEMINFORMATICS
The various companies engaged in making
use of CI are
• MDL is a CI company that enables its customers
to store, retrieve, analyze and make decision based
on chemical structures. Also it links BI and CI
world.

• Tripos also a CI company focusing mainly on

chemical information and chemical properties for
compounds involved in the early drug discovery
stages.
The various companies engaged in making
use of CI are …
Pharmacopeia is a software company which includes a BI
arm, Genetics computer group as well as molecular
simulations, Synopsys scientific systems and oxford
molecular group . The last two business form the CI part of
pharmacopeia.

Chem Navigator has developed an application that allows

researchers to submit a precise structure for comparison
with more than one million compounds in its library.
At chem navigator website, commercially available
compounds can be identified , purchased and delivered to
the researcher promptly and efficiently.
 The various companies engaged in making use of CI are…
• Anadys pharmaceuticals is a drug discovery company
using CI for linking chemistry and biology.
Why Cheminformatics?
– The effective management of information is increasingly
recognized by both public and private sector organizations
of all sorts.
– In chemistry, information systems have long played a vital
role in pharmaceuticals , agro chemical and biotechnological
research and where there is a need to handle not only
information in traditional, textual and numeric databases,
but also databases containing information about 2D and 3D
structure of molecules.
 Recent developments such as
• Computational chemistry
• Modern combinatorial chemistry
• Drug design and discovery
• Data sequence, mining and visualisation
• Chemical database design and their management
• Chemical information sources
• Medicinal chemistry etc.,has resulted in the emergence
of the discipline of CI, which involves the creation,
retrieval, organization, dissemination and processing of
chemical information .
 Scpoe in Cheminformatics
CI is the latest area is now becoming a reality in India too
Till data advance countries like US, UK, Japan and few
European countries were working on this .
In India CI is making inroad in Indian software, Department of
Bio-Tech Govt of India , R& D organizations pharmaceuticals
and other industries too.
With thousands of jobs and crores of grants by Govt of India,
CI professionals are growing day by day not only in India but
also in abroad .
CI companies are in great need of people with knowledge of
chemistry and computer skills to handle the data generated
by chemical researchers.
 Definitions of Chemoinformatics
 In cheminformatics there are only two primary questions
i. What to test next ? and
ii. What to make next?
 The main processes within drug discovery are lead identification where lead
is something that has activity in the low micro molecular range and lead
optimization, which is the process of transforming a lead into a drug
candidate.
“Chemoinformatics is a generic term that encompasses the
design , creation, organization, management, retrieval, analysis
,dissemination, visualization and use of chemical information”

Development of effective and efficient tools that can exploit
the chemical and biological explosion.
 QSAR: Quantitative Structure Activity
Relationship
• QSAR – are mathematical relationship linking
chemical structure and pharmacological
activity in a quantitative manner for a series of
compounds , methods, which can be used in
QSAR include various regression and pattern
recognition techniques.
(i) 2D Structure Searching (ii) 3D Structure Searching

(iii) 2D Similarity Searching (iv) Current interest in 3D similarity

measures
 From chemoinformatics to cheminformatics
(….already seen)
From cheminformatics to combichem.
The drive in pharmaceutical currently and most currently in the decades to
come, is the human genome project (HGP). The information stored in our
three billion base pairs is a “gold mine” for new molecular targets to treat
diseases with huge unmark therapeutic need. eg., AIDS and Cancer

Millions of gene sequences will translate into thousands of high

throughput screens (HTS). Thousands of HTS will require millions of new
chemicals. Millions of new chemicals will require millions of input
regarding structure, purity, diversity, etc.

There is no way the technology currently available in the industry can cope
with these numbers. With the advent of combinatorial chemistry
(combichem) there is a high demand for synthetic chemists as well as
combichem and chemical information scientists.
 VIDEOS TO WATCH
• https://www.youtube.com/watch?v=HHvh1bK
rbBc&list=PL345A15F1730EE1DD&index=1
• https://www.youtube.com/watch?v=dkmYTZx
TUHM&list=PL345A15F1730EE1DD&index=8