By Dr. Nandkumar M. Kamat
Bioinformatics and Chemoinformatics :-Theory and practice
(Two modules, 2 Theory + 2 Practical credits, Total 30+30 =60 hours)
Objectives: Module I Bioinformatics
Understand the nature of biological data and need for Biological databases , explore the major biomolecular sequence databases (organization and contents) and their respective search engines and database appreciate the need and significance of sequence analysis and the bioinformatics approaches for the same, application of software analysis tools to sequence data, Understanding the levels of structure organization of macromolecules and related methods of structure determination, Knowledge of various methods of structure prediction, Understanding the interaction between macromolecules, To know the approaches for structure analysis, To get basic understanding of molecular modeling and its application, Understanding the levels of structure organization of macromolecules and related methods of structure determination, Understanding the interaction between macromolecules.
Objectives: Module II Chemoinformatics
1. Introduce major aspects of chemoinformatics, with particular emphasis on applications in modern drug discovery.
2. Provide hands-on experience in chemical enumeration, creation of databases and analysis of chemicals.
3. Develop tools that aid in the design the drugs
Theory Two modules, (15 X 2=30 hours) Two credits
Syllabus:
Module I
Bioinformatics Theory (15 hours) , One credit
1. Introduction to Bioinformatics , Nature of biological data, Overview of available Bioinformatics resources on the web, NCBI/EBI/EXPASY etc (3)
2. Biological Databases: Nucleic acid sequence databases, GenBank/EMBL/DDBJ
Protein sequence databases, SwissProt, UniProtKB, Genome databases-OMIM,
structural databases, PDB, NDB, CCSD, drived databases Prosite, BLOCKS, Pfam/Prodom, Database search engines, Entrez , SRS (3)
3. Overview/concepts in sequence analysis, Pairwise sequence alignment algorithms, Scoring matrices for Nucleic acids and proteins ,Database Similarity Searches –BLAST, FASTA
Multiple sequence alignment, PRAS, CLUSTALW (3)
4. DNA and Protein Microarrays (1)
5. Macromolecular Structure and Overview of molecular modeling Protein - Primary, Secondary, Supersecondary, Tertiary and Quaternary structure, Nucleic acid – DNA and RNA, Carbohydrates, 3D Viral structures, Methods to study 3D structure, Analysis of 3D structures (2)
6. Principles of protein folding and methods to study protein folding (1)
7. Maromolecular interactions , Protein – Protein, Protein – Nucleic acids , Protein – carbohydrates (1)
8.Introduction to Molecular modelling methods (1)
Module II
Chemoinformatics:-Theory 15 hours, one credit
1. Role of Chemoinformatics in pharmaceutical/chemical research, Integrated databases, HTS analysis, Ligand based design of compounds, Structure based design of compounds (2)
2. Overview of Structure representation systems, 2D and 3D structures, General introduction to chemical structure-hybridization, tetrahedron geometry etc, The degeneracy of isomeric SMILES and introduction to unique SMILES, Internal co-ordinates and introduction to calculation of Z matrix of simple small organic molecules. (2)
3. Chemical Databases – Design, Storage and Retrieval methods (1)
4. Introduction to database filters, property based & (drug-like)-Lipinski Rule of Five (1)
5. Search techniques, similarity searches and clustering (1)
6. Modeling of small molecules and methods for interaction mapping (1)
7. Characterization of chemicals by Class & by Pharmacophore, application in
HTS Analysis (1)
8. Introduction to pharmocophore, Identification of pharmacophore features, Building pharmacophore hypothesis, Searching databases using pharmacophores (2)
9. Overview of Quantitative Structure Activity Relationship & application to Hit to lead optimization (1)
10. Chemoinformatics tools for drug discovery-Integration of active drugs ,Optimization techniques , Filtering chemicals, In silico ADMET; QSAR approach, Knowledge-based approach (3)
Practicals (15 X 2 =30 hours) Total Two modules, Two credits
Bioinformatics Practicals
Module I:- 15 hours, One credit
Syllabus:
1. Exploring NCBI database system, querying the PUBMED and GenBank databases , EBI server and searching the EMBL Nucleotide database, Exploring & querying SWISSPROT & UniProtKB (2)
2. Pair-wise global alignments of protein and DNA sequences using Needleman-Wunsch algorithm & interpretation of results to deduce homology between the sequences, use of scoring matrices, Pair-wise local alignments of protein and DNA sequences using Smith-Waterman algorithm and interpretation of results (2)
3. Database (homology) searches using different versions of BLAST and FASTA and interpretation of the results to derive the biologically significant relationships of the query sequences (proteins/DNA) with the database sequences (3)
4. Multiple sequence alignments of sets of sequences using web-based and stand-alone version of CLUSTAL. Interpretation of results to identify conserved and variable regions and correlate them with physico-chemical & structural properties (2)
5. Exploring and using the derived databases: PROSITE, PRINTS, BLOCKS, Pfam and Prodom for pattern searching, domain searches etc. (1)
6. Search & retrieval: genomic and OMIM data at NCBI server, Exploring the Database & searches on PDB and CSD, WHATIF, Interpreting DNA and Protein microarray data (1)
7. Studying the format & content of structural databases, Molecular visualization tools :-Visualization of tertiary structures, quaternary structures, architectures and topologies of proteins and DNA using molecular visualization softwares such as RasMol, Cn3D, SPDBV, Chime, Mol4D, etc. (2)
8. Structure prediction tools and homology modeling, Comparison of the performance of the different methods for various classes of proteins, Prediction of tertiary structures of proteins using Homology Modeling approach: SWISSMODEL, SWISS-PDB Viewer (2)
Chemoinformatics Practicals
Module II:- 15 hours, One credit
Syllabus:
1. Introduction to basic chemoinformatics software/tools-ACDsketch, Chemsketch, Jchem VegaZZ etc. NCL’s moltable , Chembiofinder (3)
2. Importance of storing chemical in the form of graph, linear notation (SMILES,WLN, ROSDAL-with special emphasis on SMILES and stereochemistry- both optical and geometrical isomerism), connection tables-sd and mol files. (2)
3. Importance of 3D structure and methods available for 3D structure generation- CORINA and CONCORD (2)
4. A brief introduction to database (ISIS Base) with special emphasis on the storage of chemical in the database format. (2)
5. Substructure searching and general property calculation-rotatable bonds, hydrogen bond donor, hydrogen bond acceptor, molecular weight, molecular refractivity, molecular volume, surface area and polar surface area. (3)
6. Representing SMARTS, Recursive and Component level SMARTS and linear representation of chemical concepts like Pka, pH, Zwitterions, Functional Groups, Aromaticity (2)
7. Molecular docking-Drug docking basics (1)
References:
Module I
Bioinformatics
1. Bioinformatics: A Practical Guide to the analysis of Genes and Proteins (2nd Ed.) by Baxevanis, A.D. & Ouellettee, B., F. F., New York, John Wiley & Sons, Inc. Publications, 2002.
2. Introduction to Bioinformatics by Attwood, T.K. & Parry-Smith, D.J., Delhi, Pearson Education (Singapore) Pte.Ltd., 2001.
3. Bioinformatics: Sequence and Genome Analysis by Mount, David, New York, Cold Spring Harbor Laboratory Press, 2004.
4. Current Protocols in Bioinformatics by Baxevanis, A.D., Davison, D.B., Page, R. D. M. & Petsko, G.A., New York, John Wiley & Sons Inc., 2004.
5. Structural Bioinformatics - Methods of biochemical Analysis V. 44 by Philip E. Bourne (Editor), Helge Weissig (Editor) New Jersey. Wiley-Liss, 2003.
6. Principles of protein X-ray Crystallography by Jan Drenth, Springer-Verlag, 1994.
7. Introduction to Protein Structure by Branden, Carl & Tooze, John, Garland Publishing, 1991.
8. Molecular Modeling: Principles and Applications by Andrew Leach, Prentice Hall, 2001.
9. Computational methods for protein folding : advances in chemical physics vol. 120 by Friesner, R.A. Ed., Prigogine, L. Ed. & Rice, S.A.New York. John wiley & sons, Inc. publication, 2002.
10. Dynamics of Proteins and Nucleic Acids by J.A. McCammon and S.C. Harvey Cambridge University Press, 1087.
11. Protein Structure: A Practical approach by Creighton T. E., 1989.
12. Protein Folding by Creighton T., 1992.
13. Protein Structure Prediction: A practical approach by Sternberg M.J.E., 1996.
14. Molecular Modeling: Basic Principles and application by Hans Dieter and Didier Rognan. Wiley VeH Gmbh and Co. KGA, 2003.
15. Prediction of protein structure and the principles of protein conformation by Fasman, G.D. New York. Plenum Press, 1989.
16. Protein modules in cellular signaling edited by Heilmeyer, L. & Friedrich, P. Amsterdam . IOS Press, 2001.
17. Metal sites in proteins and models by Hill, H.A.O., Sadler, P.J. & Thomson, A.J Berlin. Springer, 1999.
18. Protein structure prediction: methods and protocols by Webster, D. M., Ed. Totowa Humana Press, 2000.
19. Modular protein domains by Gimona, G. Cesareni. & Yaffe, M. Sudol ( EDS. ), USA., Wiley-vch verlag gmbh & co.,3-527-30813-X , Aug. 2004.
20. Molecular modeling: basic principles and applications by Holtje, H.D. & Folkers, G., Weinheim, VCH, 1997.
21. Molecular Modeling: Basic Principles and application by Hans Dieter & Didier Rognan, Wiley VeH Gmbh and Co. KGA, 2003.
22. Arthur M. Lesk ( 2003) Introduction to Bioinformatics, Oxford University Press, Indian edition
23. Des Higgins and Willie Taylor (2000). Bioinformatics, Sequence, structure and databanks. A practical approach. Oxford University Press, Indian edition, Second impression, New Delhi
24. Imtiaz Alam Khan (2005). Elementary bioinformatics. Pharma Book Syndicate, Hyderabad
25. Irfan Ali Khan and Attiya Khanum (eds.) ( 2002). Emerging trends in Bioinformatics. Ukaaz Publications, Hyderabad
26. Irfan Ali Khan and Attiya Khanum (eds.) (2005). Basic concepts of Bioinformatics, Ukaaz Publications, Hyderabad
27. Irfan Ali Khan and Attiya Khanum (eds.) (2004). Introductory Bioinformatics. Ukaaz Publications, Hyderabad
28. Krane Dan, E. and Raymer M.L. (2004). Fundamental concepts of Bioinformatics. Pearson education. New Delhi. Second Indian reprint.
29. Rastogi, S.C., Medirattta, N., Rastogi. P. (2004), Bioinformatics, methods and applications, genomics, proteomics and drug discovery, Prentice hall of India, pvt. Ltd., New Delhi
30. Stephen Misener and Stephen Krawetz (eds.) (2004) Bioinformatics, methods and protocols, methods in molecular biology, Volume 132, Humana Press, New Jersey, Third Indian reprint
31. T K Atwood and D J Parry-Smith (2004) Introduction to Bioinformatics, Pearson education, New Delhi
32. Xiong, Jin (2006) Essential bioinformatics, Cambridge university press
References
Module II
Chemoinformatics
1. Chemoinformatics: Theory, Practice & Products (2009) Barry A. Bunin , Brian Siesel, Guillermo Morales Jürgen Bajorath, Springer
2. Pharmaceutical Data Mining: Approaches and Applications for Drug Discovery (2009) Konstantin V. Balakin Sean Ekins (Series Editor) , Wiley
3. Chemoinformatics: An Approach to Virtual Screening (2008), Alexandre Varnek Alexander Tropsha (Editor) , Royal Society of Chemistry
4. Chemoinformatics: Concepts, Methods, and Tools for Drug Discovery (Methods in Molecular Biology), (2004) J. bajorath (ed.) Humana Press
5. Chemoinformatics (2004) Johann Gasteiger and Thomas Engel.
6. An introduction to Chemoinformatics (2003) Andrew R. Leach and Valerie J. Gillet, Kluwer Academic Publisher,
7. Handbook of Chemoinformatics. From Data to Knowledge 92003). Johann Gasteiger.
8. Chemometrics and Chemoinformatics (2005) Barry K. Lavine, ACS Symposium series 894.
9. Molecular modelling and prediction of bioactivity (2000) by Gundertofte, K. & Jorgensen, F.S. New York. Kluwer academic publishers.
Addresses of public domain database/tools/resources/ free ware websites
1. DBGET-http://www.genome.jp/dbget/
2. LinkDB-http://www.genome.jp/dbget/linkdb.html
3. Fgenes-http://www.softberry.com/berry.phtml?topic=products
4. GeneBuilder-http://www.itb.cnr.it/sun/webgene/
5. GeneSCAN-http://genes.mit.edu/GENSCAN.html
6. GRAIL-http://compbio.ornl.gov/Grail-1.3/
7. CLC Free Workbench http://www.clcbio.com/index.php?id=28
8. BioEditor-http://bioeditor.sdsc.edu/
9. CN3D 4.1 -http://www.ncbi.nlm.nih.gov/Structure/CN3D/cn3d.shtml
10. Protein-Explorer-http://www.umass.edu/microbio/chime/pe_beta/pe/protexpl/frntdoor.htm
11. Chimera-http://www.cgl.ucsf.edu/chimera/
12. Yasara-http://www.yasara.comhttp://www.yasara.com)
13. Ribosome builder-http://rbuilder.sourceforge.net/
14. ArrayExpress-www.ebi.ac.uk/arrayexpress/
15. EPICLUST-http://ep.ebi.ac.uk/EP/
16. RasMOL-http://www.umass.edu/microbio/rasmol/
17.CHIME-www.mdl.com/chime/
