Introduction and Importance of Bioinformatics Application in DrugVaccine

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/

What is Bioinformatics (BI) ? Historical Background Why Bioinformatics is Required Core of Bioinformatics Important Applications of BI Future Prospectus of Bioinformatics

Bioinformatics mines data Db

What is Bioinformatics l l l 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

Brief History § 1953: DNA structure discovered § § § § § 1960 Assembly of protein sequence database - PIR 1977: Sanger sequencing technique developed 1979 Gen. Bank 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 (5 Mb) 1998: High throughput sequencing machine developed by PE Biosystems 2000: Drosophila genome sequenced (180 Mb) 2001: Human genome rough draft (2. 91 Bb)

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

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: 39 hrs) Kyrpides, N. (1999) Bioinformatics 15, 773 -774 wit. integratedgenomics. com/GOLD/

Growth of Swiss prot

Growth of PDB

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

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

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

Protein Structures

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

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

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

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

Drug Design based on Bioinformatics Tools § Detect the Molecular Bases for Disease l l § Detection of drug binding site Tailor drug to bind at that site Protein modeling techniques Traditional Method (brute force testing) Rational drug design techniques l l 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

Steps in Post-Genomics Transcriptomics large-scale analysis of messenger RNAs; when, where, and under what conditions genes are expressed. Proteomics study 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.

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

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