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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
10000
15000
20000
25000
30000
35000
40000
45000
50000
55000
60000
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!
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