Chemoinformatics Practical

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

[email protected]

www.puneetsclassroom.in