1. AIB
Chemical Similarity Search
28 November 2013
Dr. Puneet Kacker
www.puneetsclassroom.in

2. Chemoinformatics
AIB
 Chemoinformatics is an interface science aimed
primarily at discovering new chemical entries that will
ultimately result in the development of novel treatments
for unmet medical needs.
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3. Drug Discovery Pipeline
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A Typical Drug Discovery Workflow
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4. Where are we?
A Typical Drug Discovery Workflow
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5. Hit Identification: What is Expected
Some Magic
Database of
Chemical
Compounds
(Millions of Cmpds)
??
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Few Compounds
Ready for
Synthesis/Testing
Magic of Chemical Similarity
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6. Chemical Similarity
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Similarity
Common
Substructure
Overall Similarity
Ligand-based
Methods
Similar Predicted
Activity
Similar Fitting into
Binding Pocket
Structure-based
Method
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7. Chemical Search Methods
Substructure search
Similarity
Docking
QSAR
Three things should be kept in Mind:
1. Question
2. Model
3. Requirements
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8. Substructure Search
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Question: Which molecules in a database
contain the specified substructure?
Model: Compounds that contain this
substructure are likely to be active.
Query requires: 2D or 3D substructure
common to actives (‘pharmacophore’ in
3D).
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9. Similarity Based Search
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Question: Which molecules in a database
are ‘similar’ to the query molecule(s)?
Model: Compounds globally similar in
structure to the query are likely to have a
similar activity.
Query requires: One or more active
molecules.
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10. Docking Based Search
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Question: Which molecules in a database
can fit into the binding site of a known
enzyme or receptor?
Model: Compounds that have a high
interaction score are likely to bind to the
enzyme.
Query requires: Atomic-level structure of
receptor (or model built from homolog).
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11. QSAR Based Method
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Question: Which molecules have the
highest predicted activity?
Model: Compounds with high predicted
activity are likely to be active.
Query requires: Activity data on enough
compounds to form QSAR.
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12. Where to Search?
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Databases
PubChem
ZINC
Collaborative
Collection
BindingDB
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13. Databases: NCBI PubChem
pubchem.ncbi.nlm.nih.gov/
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14. PubChem Results
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Search for
Similar Compounds Scores >=95%
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15. ZINC Database
http://zinc.docking.org/
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16. AIB
PubChem Chemical Similarity Search Tool
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17. Keyword Based Search
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18. Identity/Similarity: Structure Draw
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19. Identity/Similarity: CID/SMILES/InChI
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20. Identity/Similarity: Structure File
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21. Substructure Based Search: Structure Draw
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22. Substructure Based Search:
SMILES/CID/InChI
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23. Substructure Based Search: Structure File
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24. Molecular Formula Based Search
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25. 3D Conformer
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26. PubChem: Limit
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27. Chemical Sketching
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28. Books
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29. Food for Thought
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30. Smart Apps for Your Smartphone
iMolview
By Molsoft
ChemDoodle Mobile
By iChemLabs, LLC.
ChemDraw
By PerkinElmer
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31. Exercise-I
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Warfarin
Anticoagulant, Vitamin K Epoxide Reductase Inhibitor
Draw the structure of Warfarin using eMolecules
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32. Exercise-II
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Warfarin
Find out similar structures of Warfarin using PubChem Chemical Similarity Search
Also try to Download Results in SDF Format
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33. AIB
Questions?
-:Contact:Room Number LG-16, J3 Block
Amity Institute of Biotechnology
Amity University Uttar Pradesh
Noida-201313
pkacker@amity.edu
www.puneetsclassroom.in