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AIB
Chemical Similarity Search
28 November 2013
Dr. Puneet Kacker
www.puneetsclassroom.in
AIBChemoinformatics
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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AIBDrug Discovery Pipeline
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A Typical Drug Discovery Workflow
AIBWhere are we?
A Typical Drug Discovery Workflow
AIBHit Identification: What is Expected
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Database of Chemical
Compounds(Millions of Cmpds)
Few Compounds Ready for
Synthesis/Testing
Some Magic
??
Magic of Chemical Similarity
AIBChemical Similarity
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Similarity
Common Substructure
Overall SimilaritySimilar Predicted
ActivitySimilar Fitting into
Binding Pocket
Ligand-based Methods
Structure-based Method
AIBChemical Search Methods
Substructure searchSimilarityDockingQSAR
Three things should be kept in Mind:1. Question2. Model3. Requirements
AIBSubstructure Search
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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AIBSimilarity Based Search
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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AIBDocking Based Search
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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AIBQSAR Based Method
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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AIBWhere to Search?
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Databases
PubChem ZINCCollaborative
CollectionBindingDB
AIBDatabases: NCBI PubChem
13pubchem.ncbi.nlm.nih.gov/
AIBPubChem Results
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Search forSimilar Compounds Scores >=95%
AIBZINC Database
15http://zinc.docking.org/
AIB
PubChem Chemical Similarity Search Tool
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AIBKeyword Based Search
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AIBIdentity/Similarity: Structure Draw
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AIBIdentity/Similarity: CID/SMILES/InChI
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AIBIdentity/Similarity: Structure File
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AIBSubstructure Based Search: Structure Draw
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AIBSubstructure Based Search:
SMILES/CID/InChI
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AIBSubstructure Based Search: Structure File
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AIBMolecular Formula Based Search
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AIB3D Conformer
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AIBPubChem: Limit
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AIBChemical Sketching
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AIBBooks
AIBFood for Thought
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AIBSmart Apps for Your Smartphone
ChemDrawBy PerkinElmer
iMolviewBy Molsoft
ChemDoodle MobileBy iChemLabs, LLC.
AIBExercise-I
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WarfarinAnticoagulant, Vitamin K Epoxide Reductase Inhibitor
Draw the structure of Warfarin using eMolecules
AIBExercise-II
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Warfarin
Find out similar structures of Warfarin using PubChem Chemical Similarity SearchAlso try to Download Results in SDF Format
AIB
Questions?
-:Contact:-Room Number LG-16, J3 BlockAmity Institute of BiotechnologyAmity University Uttar Pradesh
www.puneetsclassroom.in
