BIOINFORMATICS INTRODUCTION

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INVESTIGATION OF BIOLOGICAL SYSTEMS BIOLOGICAL INFORMATION DATA COLLECTION, CLASSIFICATION, ORGANIZATION AND INTERCONNECTIONS INFORMATION PACKAGE UTILITY

Total length of DNA ~ 2 x 1014 kmCircumference of the earth 4 x 104 kmDistance between the earth and the sun 1.5 x 108 km : 

Total length of DNA ~ 2 x 1014 kmCircumference of the earth 4 x 104 kmDistance between the earth and the sun 1.5 x 108 km

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GENOME: Total DNA in an organism Human genome ~ 3 bi bp Worm 100 mi bp Fruit fly 160 mi bp Yeast 15 mi bp

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Genomics Application of high throughput automated molecular biology technologies Study of large number of genes & gene products taking advantage of complete genome sequence All at once in whole cells, whole tissues or whole organism A who listic or systems approach to the study of information flow within a cell Knowledge of specific genes underlying diseases & differences in Individual’s genetic make up that respond to differently to drugs, are changing the face of drug development & delivery

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323 bacterial genome have been sequenced 235 sequences belong to different species 65 sequences of type strains 32 sequenced more than once of the same species 1350 more sequencing projects in progress Impact of bacterial genomics bioinformatics second generation genomic technologies on target identification assay development lead optimization compound characterization

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First genome sequence of a complete organism (bacterium): Haemophilus influenza,1995 first free-living organism Mycoplasma genitalium, 1995 470 proteins First genome sequence of a complete multicellular organism: Caenorhabditis elegans, 1998 ~18,000 proteins First genome sequence of an archaeum: Methanococcus jannaschii, 1995 ~1,700 proteins Human genome sequence: 2001 25-30,000 proteins second mammal, mouse genome - others- over 300s of bacteria/archaea, plants, animals, zebrafish - - provides complete information about what makes up an organism but: we know the functions of <50% of all genes Genomics: a revolution in the making

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Genome Ordered library Random small-insert library of one clone Random small-insert library of whole genome Sequence and contig assembly Repeat for other clones Assemble complete genome sequence Sequence and contig assembly Assemble complete genome sequence Clone- by- clone-approach Shotgun sequence SEQUENCING

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FIRST-GENERATION GEL-BASED SEQUENCE ANALYSIS Capable of sequencing small regions Y chromosome: 50 Mb; Chromosome 1: 250 Mb 50,000 -100,000 b/year @ $1-2/b SECOND-GENERATION SEQUENCING TECHNOLOGIES Sequence 100,000 b/d @ $ 0.20 to 0.50/b Faster, more sensitive, accurate THIRD-GENERATION GEL-LESS TECHNOLOGIES Fluorescence detection of bases by flow cytometry Scanning tunneling or atomic force microscopies Mass spectroscopic analysis Sequencing by hybridization

Functions of protein : 

Functions of protein

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NUCLEIC ACIDS PROTEINS 4 NUCLEOTIDES 20 AMINO ACIDS 4 100 = 2 200 20100 = 2420 4 2 = 16 20 2 = 400

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TRI-PEPTIDE + AMINO ACIDS DI-PEPTIDE H2O POLYPEPTIDE

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GENETIC CODE

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The primary structure of a protein is its linear sequence of amino acids and the location of any disulfide (-S-S-) bridges.

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SECONDARY STRUCTURE Most proteins contain one or more stretches of amino acids that take on a characteristic structure in 3-D space. The most common of these are the alpha helix and the beta conformation. Alpha Helix The R groups of the amino acids all extend to the outside. The helix makes a complete turn every 3.6 amino acids. The helix is right-handed; it twists in a clockwise direction. The carbonyl group (-C=O) of each peptide bond extends parallel to the axis of the helix and points directly at the -N-H group of the peptide bond 4 amino acids below it in the helix. A hydrogen bond forms between them [-N-H·····O=C-] .

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ALPHA HELIX

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BETA CONFORMATION Consists of pairs of chains lying side-by-side and Stabilized by hydrogen bonds between the carbonyl oxygen atom on one chain and the -NH group on the adjacent chain. The chains are often "anti-parallel"; the N-terminal to C-terminal direction of one being the reverse of the other

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FOUR-RESIDUE B-HAIRPINS These are also quite common with the first two residues adopting the alpha-helical conformation. The third residue has psi and phi angles which lie in the bridging region between alpha-helix and beta-sheet and the final residue adopts the left-handed alpha-helical conformation and is therefore usually glycine, aspartate or asparagine.

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TERTIARY PROTEIN STRUCTURE AND FOLDS There are a number of examples of small proteins (or peptides) which consist of little more than a single helix. A striking example is alamethicin, a transmembrane voltage gated ion channel, acting as a peptide antibiotic.

Quaternary Structure of Protein : 

Quaternary Structure of Protein

Structures of Proteins : 

Structures of Proteins

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FOUR NUCLEOTIDES OF DNA DNA-1 ATGAAGGCCTTAAAAGAGCTTTCCCAATTTCTAG.. DNA-2 GGTTAACGTTAGGGGGAACCAAGTGGAATTGATA.. A T G C

DNA MICRO ARRAY : 

DNA MICRO ARRAY

Sickle cell anaemia- due to change in one base pairCCTGATCC (Valine) – CCTGTTCC(Glutamine) : 

Sickle cell anaemia- due to change in one base pairCCTGATCC (Valine) – CCTGTTCC(Glutamine)