印度昌迪加爾市微生物技術(shù)研究所生物信息學(xué)課件bic

1、Introduction and Importance of Bioinformatics: Application in Drug/Vaccine DesignG. P. S. Raghava Email: raghavaimtech.res.in Web: What is Bioinformatics (BI) ? Historical Background Why Bioinformatics is RequiredCore of BioinformaticsImportant Applications of BI Future Prospectus of BioinformaticsB

2、ioinformatics mines data DbWhat is Bioinformatics puting: Application of Computer in Biosciences puting started in 1960sExplosion of Genomic DataAccess and Management of Data puting+Information ScienceRole of Internet in BIBrief History1953: DNA structure discovered1960 Assembly of protein sequence

3、database - PIR1977: Sanger sequencing technique developed1979 GenBank prototype was conceived1980 EMBL database was founded1988: Human Genome project initiated1993 The first genome database ACEDB (C. elegans)1995: Influenza genome sequenced (5Mb)1998: High throughput sequencing machine developed by

4、PE Biosystems2000: Drosophila genome sequenced (180Mb)2001: Human genome rough draft (2.91Bb)Why Bioinformatcs is RequiredData growth is exponentialDifficult to understand life without BIDetection of new diseasesBI tools allow to save expr. Expend.Rational Drug design Computer-aided vaccine designGO

5、LD:Genome Online Database Published Complete Genomes: 93- 16 Archaeal- 65 Bacterial- 12 Eukaryal On-going:- Prokaryotes: 284- Eukaryotes : 195Last update: 17 June 2002 (14:39hrs)Kyrpides, N. (1999) Bioinformatics 15, 773-774 /GOLD/Growth of Swiss protGrowth of PDBGrowth of gene-driven researchOne pa

6、per every five minutesApplication of BioinformaticsGenome AnnotationProtein Structure PredictionProteomicsDNA Chip technologyDisease DiagnosticsFingerprinting TechniqueDrug/Vaccine Design Genome AnnotationThe Process of Adding Biology Information andPredictions to a Sequenced Genome FrameworkProtein

7、 Structures Protein Structure PredictionExperimental TechniquesX-ray Crystallography NMRLimitations of Current Experimental TechniquesProtein DataBank (PDB) - 17000 protein structuresSwissProt - 90,000 proteinsNon-Redudant (NR) - 800,000 proteinsImportance of Structure PredictionFill gap between kno

8、wn sequence and structures Protein Engg. To alter function of a proteinRational Drug DesignTraditional Proteomics1D gel electrophoresis (SDS)2D gel electrophoresisProtein ChipsChips coated with proteins/Antibodieslarge scale version of ELISAMass SpectrometryMALDI: Mass fingerprintingElectrospray and

9、 tandem mass spectrometrySequencing of Peptides (N-C)Matching in Genome/Proteome DatabasesFingerprinting TechniqueWhat is fingerprintingIt is technique to create specific pattern for a given organism/personTo compare pattern of query and target objectTo create Phylogenetic tree/classification based

10、on patternType of FingerprintingDNA FingerprintingMass/peptide fingerprintingProperties based (Toxicity, classification)Domain/conserved pattern fingerprinting Common ApplicationsPaternity and Maternity Criminal Identification and Forensics Personal Identification Classification/Identification of or

11、ganismsClassification of cellsBioinformatics Approach for Identification of Vaccine CandidateIdentification of the vaccine candidates (Antigenic Region) for designing subunit vaccine.Antigen degraded in peptides by proteasomeMHC Molecule bind to antigenic peptideMHC+peptide to cell surfacePrediction

12、 of Promiscuous MHC binding peptides.Prediction Method for T-Cell Epitopes.Molecular MimicryModel Studies on HIV and M.tuberculosisDrug Design based on Bioinformatics ToolsDetect the Molecular Bases for DiseaseDetection of drug binding siteTailor drug to bind at that siteProtein modeling techniquesT

13、raditional Method (brute force testing) Rational drug design techniquesScreen likely compounds built Modeling large number of compounds (automated)Application of Artificial intelligenceLimitation of known structuresSearch of Target proteinSearch of Lead compoundSteps in Post-Genomics Transcriptomics

14、 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 protei

15、ns 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 f