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Chemoinformatics
Harno Dwi Pranowo, Prof. Dr.
Chemistry Department FMIPA UGM
Computation
Oracle Database (HTS)
 All the compounds pass the
 Compounds were tested
Lipinksi Rule of Five and toxicity
filters
against related assays and
showed activity, including
selectivity within target families
Excel Spreadsheet (Toxicity)
 One of the compounds was
previously tested for toxicology
and was found to have no liver
toxicity
Oracle Database (Genomics)
 None of these compounds
Word Document (Chemistry)
have been tested in a microarray
assay
 Several of the compounds had
?
Computation
SCIENTIST
 The information in the
structures and known activity
data is good enough to create a
QSAR model with a confidence of
75%
been followed up in a previous
project, and solubility problems
prevented further development
Journal Article
 A recent journal article
“These compounds look promising from their
HTS results. Should I commit some chemistry
resources to following them up?”
reported the effectiveness of
some compounds in a related
series against a target in the
same family
External Database (Patent)
Word Document (Marketing)
 Some structures with a
 A report by a team in
similarity > 0.75 to these appear
to be covered by a patent held by
a competitor
Marketing casts doubt on
whether the market for this
target is big enough to make
development cost-effective
THREE BROAD TECHNOLOGIES ARE DRIVING DRUG DISCOVERY
•Study of both structural and
functional aspects of the
genome, including both genes
and proteins, leading to a
greater understanding of
cellular processes and disease
GENOMICS
Supported by
BIOINFORMATICS
•Rapid and systematic
generation of a variety of
molecular entities, or
building blocks, in many
different or unique
combinations
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CATALYTIC/
COMBINATORIAL
CHEMISTRY
HIGH THROUGHPUT
SCREENING
•Use of robotic automation to
allow for massive parallel
experimentation and testing
of many compounds or
targets
“A chemoinformatician is a machine …..…”
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From chemical documentation to
chemoinformatics
• Chemical documentation is long established
– Chemisches Journal started in 1778
– Chemical Abstracts started in 1907
• First computer-based information systems and
services in Sixties
– Chemical Titles in 1961
– Morgan and Sussenguth algorithms in 1965
• Recent emergence of chemoinformatics
– M. Hann and R. Green (1999), Chemoinformatics - a
new name for an old problem?, Curr. Opin. Chem. Biol.,
Vol. 3, pp. 379-383.
Chemoinformatics: definitions
• “The use of information technology and 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 drug lead identification and optimization”
F.K. Brown (1998), Chemoinformatics: What is it and how does it
impact drug discovery?, Ann. Reports Med. Chem., Vol. 33, pp.
375-384
• Take 1998 as the starting point for the bibliometric analyses
• Many alternatives, e.g.
 “Chemoinformatics is a generic term that encompasses the
design, creation, organization, management, retrieval,
analysis, dissemination, visualization and use of chemical
information”
G Paris (August 1999 ACS meeting),
 “Chemoinformatics is the application of informatics methods
to solve chemical problems” J. Gasteiger and T. Engels (2003),
Chemoinformatics: a Textbook, Wiley-VCH.
Chemoinformatics hits on Google
400000
Cheminformatics
350000
Chemoinformatics
Total
300000
Dec 2005
348,100
250000
200000
April 2005
125,600
150000
100000
50000
July 2000
723
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Number of word occurrences on Google, Taken from http://www.molinspiration.com/chemoinformatics.html
Chemoinformatics-What is it?
• Use of computer and informational
techniques, applied to a range of problems
in the field of chemistry.
• This in silico techniques are used in
pharmaceutical companies in the process
of drug discovery.
Frank Brown’s Definition
• …the mixing of information resources to
transform data into information and
information into knowledge, for the intended
purpose of making decisions faster in the
arena of drug lead identification and
optimisation.
– Brown, F.K. “Chemoinformatics, what it is and how does it impact drug
discovery.” Annual Reports in Medicinal Chemistry, 1998, 33, 375-384.
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Chemoinformatics-What is it?
Chemoinformatics-What is it?
• Boundaries between bioinformatics and
chemoinformatics are fluid
– Both should be closely combined or merged to
significantly impact biotechnology or
pharmaceutical research
Bajorath, Jürgen, Ed. Chemoinformatics: Concepts, Methods, and
Tools for Drug Discovery. (Methods in Molecular Biology; 275)
Humana Press: Totawa, NJ, 2004.
Chemical Informatics
Chemical Informatics: the application of
information technology to chemistry (not with
a specific focus on drug discovery)
Chemical informatics is the application of
information technology to help chemists
investigate new problems and organize,
analyze, and understand scientific data in the
development of novel compounds, materials,
and processes.
Major aspects of chemical informatics
– Information Acquisition: Methods for generating
and collecting data empirically (experimentation)
or from theory (molecular simulation)
– Information Management: Storage and retrieval of
information
– Information Use: Data Analysis, correlation, and
application to problems in the chemical and
biochemical sciences
Chemometrics
• Chemometrics
– Application of statistical methods to chemical data
and the derivation of relevant statistical models
and descriptors
– Increasingly difficult to distinguish between
chemometrics and chemoinformatics
Dmitrii Ivanovich Mendeleev,
1834-1907
Discoverer of the Periodic Table—
An Early “Chemoinformatician”
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Why Mendeleev?
Faced with a large amount of data, with many
gaps, Mendeleev:
– Sought patterns where none were obvious,
– Made predictions about properties of unknown
chemical substances, based on observed
properties of known substances,
– Created a great visualization tool!
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The Periodic Table of the Elements by
Mark Winter
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Molecular descriptors and chemical spaces
• There are no generally preferred descriptor spaces.
• Require to generate reference spaces for specific
application on a case by case
Application of Cheminformatics
in the Drug Industry
• The computer is used to analyze the
interactions between the drug and the
receptor site and design molecules with an
optimal fit.
• Once targets are developed, libraries of
compounds are screened for activity with one
or more relevant assays using High
Throughput Screening.
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Application of Cheminformatics
in the Drug Industry
• Hits are then evaluated for binding, potency,
selectivity, and functional activity.
• Seeking to improve:
– Potency
– Absorption
– Distribution
– Metabolism
– Elimination
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Characteristics of a Chemical
Informatics researchers
• Appreciates the value of algorithms
• Is interested in data mining, data modeling,
and relational database systems
• Pays attention to searching issues and the
literature
• Has compatibility and commonality with
bioinformatics research
• Is able to talk to computer scientists.
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Major Journals
• Journal of Chemical Information and Computer
Sciences (ACS): to split in 2005 into:
– Journal of Chemical Information and Modeling
– Journal of Chemical Theory and Computation
• Journal of Molecular Graphics and Modelling
(Elsevier)
• Journal of Combinatorial Chemistry (ACS)
• Journal of Proteome Research (ACS)
• Proteomics (Wiley-VCH)
• Molecular and Cellular Proteomics (ASBMB)
• Acta Crystallographica (IUCr)
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Chemical Informatics Textbooks
• Leach, Andrew R.; Gillet, Valerie J. An Introduction to
Chemoinformatics. Kluwer, 2003. ISBN 1-40201347-7
• Gasteiger,Johann;Engel, Thomas. Chemoinformatics:
A Textbook. Wiley-VCH, 2003. ISBN 3-527-30681-1
• Bajorath, Jürgen, Ed. Chemoinformatics: Concepts,
Methods, and Tools for Drug Discovery. (Methods in
Molecular Biology; 275) Humana, 2004. ISBN 158829-261-4
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Reference Works
• Encyclopedia of Computational Chemistry, Schleyer, P. von R.;
Allinger, N.L.; Clark, T.; Gasteiger, J.; Kollman, P.A.; Schaefer,
H.F.; Shreiner, P.R. (Eds.). 5 v. Wiley, Chichester, 1998.
• Gasteiger, Johann J., ed. Handbook of Chemoinformatics: From
Data to Knowledge. 4 v. Wiley-VCH, 2003. ISBN 3-527-30680-3
• Reviews in Computational Chemistry. Wiley-VCH, 1990• Paris, Greg. Bibliography: Chemical Information Retrieval and
3D Searching.
http://panizzi.shef.ac.uk/cisrg/links/grep/chemDB.4.html
• SIRCh: Chemical Informatics Home Page at Indiana University
http://www.indiana.edu/~cheminfo/informatics/cinformhome.
html
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Conclusion
• Chemical Informatics is an evolving field with
many facets.
• It will become increasingly important in areas
of chemistry outside the drug industry.
• It will play an increasing role in the developing
area of proteomics.
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Open Source / Free Software
• Blue Obelisk - http://wiki.cubic.unikoeln.de/dokuwiki/doku.php
• InChI - http://www.iupac.org/inchi/
• JMOL – http://jmol.sourceforge.net
• FROWNS - http://frowns.sourceforge.net/
• OpenBabel - http://openbabel.sourceforge.net/
• CML - http://cml.sourceforge.net/
• CDK - http://almost.cubic.uni-koeln.de/cdk/
• MMTK http://starship.python.net/crew/hinsen/MMTK/
Yahoo! Chemoinformatics Discussion List
• For
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Job postings
Ideas exchange
Questions
Industry – Student connections
To join, go to http://groups.yahoo.com/group/chemoinf
Or send an email to [email protected]