Chemoinformatics Practical
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This document discusses chemical similarity search methods for identifying new drug candidates. It describes the typical drug discovery workflow involving searching large databases of chemical compounds for structures similar to known active molecules. The main methods discussed are substructure search, similarity search, molecular docking and QSAR. Popular databases mentioned for searching include PubChem, ZINC and BindingDB. Examples are given of using PubChem's chemical similarity search tool to find structures similar to the drug Warfarin.
Chemoinformatics Practical
- 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. 2
- 3. Drug Discovery Pipeline AIB A Typical Drug Discovery Workflow 3
- 4. Where are we? A Typical Drug Discovery Workflow AIB
- 5. Hit Identification: What is Expected Some Magic Database of Chemical Compounds (Millions of Cmpds) ?? AIB Few Compounds Ready for Synthesis/Testing Magic of Chemical Similarity 5
- 6. Chemical Similarity AIB Similarity Common Substructure Overall Similarity Ligand-based Methods Similar Predicted Activity Similar Fitting into Binding Pocket Structure-based Method 6
- 7. Chemical Search Methods Substructure search Similarity Docking QSAR Three things should be kept in Mind: 1. Question 2. Model 3. Requirements AIB
- 8. Substructure Search AIB 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). 8
- 9. Similarity Based Search AIB 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. 9
- 10. Docking Based Search AIB 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). 10
- 11. QSAR Based Method AIB 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. 11
- 14. PubChem Results AIB Search for Similar Compounds Scores >=95% 14
- 16. AIB PubChem Chemical Similarity Search Tool 16
- 21. Substructure Based Search: Structure Draw AIB 21
- 23. Substructure Based Search: Structure File AIB 23
- 24. Molecular Formula Based Search AIB 24
- 28. Books AIB
- 30. Smart Apps for Your Smartphone iMolview By Molsoft ChemDoodle Mobile By iChemLabs, LLC. ChemDraw By PerkinElmer AIB
- 31. Exercise-I AIB Warfarin Anticoagulant, Vitamin K Epoxide Reductase Inhibitor Draw the structure of Warfarin using eMolecules 31
- 32. Exercise-II AIB Warfarin Find out similar structures of Warfarin using PubChem Chemical Similarity Search Also try to Download Results in SDF Format 32
- 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
Editor's Notes
- #16: Snapshot for the types of library available on zinc database. And also total number of compounds available in each of the database