Introduction and Importance of Bioinformatics: Application in Drug/Vaccine Design G. P. S. Raghava

1. Introduction and Importance of Bioinformatics: Application in Drug/Vaccine Design G. P. S. Raghava Email: raghava@imtech.res.in Web: http://www.imtech.res.in/raghava/

2. What is Bioinformatics (BI) ? Historical Background Why Bioinformatics is RequiredCore of BioinformaticsImportant Applications of BI Future Prospectus of Bioinformatics

3. Bioinformatics mines data Db

4. What is Bioinformatics • Biocomputing: Application of Computer in Biosciences • Biocomputing started in 1960’s • Explosion of Genomic Data • Access and Management of Data • Biocomputing+Information Science • Role of Internet in BI

5. Brief History • 1953: DNA structure discovered • 1960 Assembly of protein sequence database - PIR • 1977: Sanger sequencing technique developed • 1979 GenBank prototype was conceived • 1980 EMBL database was founded • 1988: Human Genome project initiated • 1993 The first genome database ACEDB (C. elegans) • 1995: Influenza genome sequenced (5Mb) • 1998: High throughput sequencing machine developed by PE Biosystems • 2000: Drosophila genome sequenced (180Mb) • 2001: Human genome rough draft (2.91Bb)

6. Why Bioinformatcs is Required • Data growth is exponential • Difficult to understand life without BI • Detection of new diseases • BI tools allow to save expr. Expend. • Rational Drug design • Computer-aided vaccine design

8. GOLD:Genome Online Database Published Complete Genomes: 93 - 16 Archaeal - 65 Bacterial - 12 Eukaryal On-going: - Prokaryotes: 284 - Eukaryotes : 195 Last update: 17 June 2002 (14:39hrs) Kyrpides, N. (1999) Bioinformatics 15, 773-774 wit.integratedgenomics.com/GOLD/

9. Growth of Swiss prot

10. Growth of PDB

11. Growth of ‘gene-driven’ research One paper every five minutes

14. Application of Bioinformatics • Genome Annotation • Protein Structure Prediction • Proteomics • DNA Chip technology • Disease Diagnostics • Fingerprinting Technique • Drug/Vaccine Design

15. Genome Annotation The Process of Adding Biology Information and Predictions to a Sequenced Genome Framework

16. Protein Structures

17. Protein Structure Prediction • Experimental Techniques • X-ray Crystallography • NMR • Limitations of Current Experimental Techniques • Protein DataBank (PDB) -> 17000 protein structures • SwissProt -> 90,000 proteins • Non-Redudant (NR) -> 800,000 proteins • Importance of Structure Prediction • Fill gap between known sequence and structures • Protein Engg. To alter function of a protein • Rational Drug Design

18. Traditional Proteomics • 1D gel electrophoresis (SDS-PAGE) • 2D gel electrophoresis • Protein Chips • Chips coated with proteins/Antibodies • large scale version of ELISA • Mass Spectrometry • MALDI: Mass fingerprinting • Electrospray and tandem mass spectrometry • Sequencing of Peptides (N->C) • Matching in Genome/Proteome Databases

19. Fingerprinting Technique • What is fingerprinting • It is technique to create specific pattern for a given organism/person • To compare pattern of query and target object • To create Phylogenetic tree/classification based on pattern • Type of Fingerprinting • DNA Fingerprinting • Mass/peptide fingerprinting • Properties based (Toxicity, classification) • Domain/conserved pattern fingerprinting • Common Applications • Paternity and Maternity • Criminal Identification and Forensics • Personal Identification • Classification/Identification of organisms • Classification of cells

20. Bioinformatics Approach for Identification of Vaccine Candidate Identification of the vaccine candidates (Antigenic Region) for designing subunit vaccine. • Antigen degraded in peptides by proteasome • MHC Molecule bind to antigenic peptide • MHC+peptide to cell surface • Prediction of Promiscuous MHC binding peptides. • Prediction Method for T-Cell Epitopes. • Molecular Mimicry • Model Studies on HIV and M.tuberculosis

21. Drug Design based on Bioinformatics Tools • Detect the Molecular Bases for Disease • Detection of drug binding site • Tailor drug to bind at that site • Protein modeling techniques • Traditional Method (brute force testing) • Rational drug design techniques • Screen likely compounds built • Modeling large number of compounds (automated) • Application of Artificial intelligence • Limitation of known structures • Search of Target protein • Search of Lead compound

22. Steps in Post-Genomics •Transcriptomics large-scale analysis of messenger RNAs; when, where, and under what conditions genes are expressed. •Proteomicsstudy of protein expression in time and space, more important than gene expression studies to whats actually happening in the cell. •Structural genomics 3-D structures of one or more proteins from each protein family, clues to function and biological targets for drug design. •Knockout studies experimental method for understanding the function of DNA sequences and the proteins they encode. Inactivate genes in living organisms and monitor any changes, reveal the function of specific genes. Majority of knockouts do not give null phenotype. •Comparative genomics DNA sequence patterns of humans and well-studied model organisms, most powerful strategies for identifying human genes and interpreting their function.

23. Business Opportunities in BI • Software development • Web servers development • Train manpower in Field of BI • Database management • Rational Drug design • Develop Diagnostic kits • Assist user in Vaccine development • Consultant to Biotech Companies

24. THANK YOU!