Introduction and Importance of Bioinformatics: Application in

Drug/Vaccine Design

G. P. S. RaghavaG. P. S. Raghava

Email: raghava@imtech.res.in Email: raghava@imtech.res.in Web: http://www.imtech.res.in/raghava/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

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 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)

Why Bioinformatcs is Required

Data growth is exponentialDifficult to understand life without BIDetection of new diseasesBI 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 (14:39hrs)Kyrpides, N. (1999) Bioinformatics 15, 773-774

wit.integratedgenomics.com/GOLD/

Growth of Swiss prot

Growth of PDB

1982 1984 1986 1988 1990 1992 1994 1996 1998 20000

5000

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15000

20000

25000

30000

35000

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Number of papers including the word "gene"

Growth of ‘gene-driven’ research

One paper every five minutes

Application of Bioinformatics

Genome AnnotationProtein Structure PredictionProteomicsDNA Chip technologyDisease DiagnosticsFingerprinting TechniqueDrug/Vaccine Design

Genome Annotation

The Process of Adding Biology Information and

Predictions to a Sequenced Genome Framework

Protein Structures

Protein Structure PredictionExperimental 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

Traditional Proteomics

1D gel electrophoresis (SDS-PAGE)2D gel electrophoresisProtein 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

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

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

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

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.

Business Opportunities in BI

Software development Web servers developmentTrain manpower in Field of BI Database managementRational Drug designDevelop Diagnostic kitsAssist user in Vaccine developmentConsultant to Biotech Companies

THANK YOU!