BioInformatics (1)

What is Life All About : Self-compiling & self-assembling Complementary surfaces Watson-Crick base pair (Nature April 25, 1953)

Life Science vs Computing Where do parasites come from? (computer & biological viral codes) Over $12 billion/year on computer viruses LoveBug Set dirtemp =3D fso.GetSpecialFolder(2) Set c =3D fso.GetFile(WScript.ScriptFullName) c.Copy(dirsystem&"\MSKernel32.vbs") c.Copy(dirwin&"\Win32DLL.vbs") c.Copy(dirsystem&"\LOVE-LETTER-FOR-YOU.TXT.vbs") regruns() html() spreadto () listadriv() 20 M dead (worse than black plague & 1918 Flu) AIDS - HIV-1 Polymerase drug resistance mutations M41L, D67N, T69D, L210W, T215Y, H208Y PISPIETVPV KLKPGMDGPK VKQWPLTEEK IKALIEICAE LEKDGKISKI GPVNPYDTPV FAIKKKNSDK WRKLVDFREL NKRTQDFCEV

Concept Computers Organisms Instructions Program Genome Bits 0,1 a,c,g,t Stable memory ROM,Disk,tape DNA Active memory RAM RNA Processing CPU/Compiler enzyme/Ribosome Editing Editor tRNA Environment Sockets,people Water,salts,heat I/O AD/DA proteins Monomer Minerals Nucleotide Polymer chip DNA,RNA,protein Replication Cut/Paste DNA replication Sensor/In scanner Chem/photo receptor Exciting Life ??

of RNA-based life: C,H,N,O,P Useful for many species: Na, K, Fe, Cl, Ca, Mg, Mo, Mn, S, Se, Cu, Ni, Co, Si Elements

The Four Nucleosides of DNA dA dG dC dT A nucleoside is a sugar, here deoxyribose, plus a base dA = deoxyadenosine, etc. PYRIMIDINESPURINES

Adenine Guanine ThymineCytosineUracil BASES

Base Pairing

A nucleotide is a phospate, a sugar, and a purine or a pyramidine base. The monomeric units of nucleic acids are called nucleotides.

Chromosomes

Genome and gene

Nucleic acid and proteins

Nucleotide codes

Amino acid codes

Standard Genetic Code

Schematic illustration of a plant cell (Home for DNA)

History of structure determination for nucleic acids and proteins

Human chromosomes: idiograms

X-linked recessive disorder. The inheritance pattern is shown for a recessive gene on the chromosome X, designated in bold. Male XY (normal) FemaleX (normal) Female XX (normal) Female XX (normal) Male XY (normal) Male XY (affected)

Reductionistic and synthetic approaches in biology Biological System (Organism) Building Blocks (Genes/Molecules) Synthetic Approach (Bioinformatics) Reductionistic Approach (Experiments)

Basic principles in physics, chemistry and biology. Principles Known? Physics Matter Chemistry Compound Biology Organism Elementary Particles Yes Elements Yes Genes No

The addresses for the major databases

New generation of molecular biology databases

Example of sequence database entry for Genbank LOCUSDRODPPC4001 bpINV15-MAR-1990 DEFINITIOND.melanogaster decapentaplegic gene complex (DPP-C), complete cds. ACCESSIONM30116 KEYWORDS. SOURCED.melanogaster, cDNA to mRNA. ORGANISMDrosophila melanogaster Eurkaryote; mitochondrial eukaryotes; Metazoa; Arthropoda; Tracheata; Insecta; Pterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophilia. REFERENCE1 (bases 1 to 4001) AUTHORSPadgett, R.W., St Johnston, R.D. and Gelbart, W.M. TITLEA transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-beta family JOURNALNature 325, (1987) MEDLINE COMMENTThe initiation codon could be at either or FEATURESLocation/Qualifiers source /organism=“Drosophila melanogaster” /db_xref=“taxon:7227” mRNA< /gene=“dpp” /note=“decapentaplegic protein mRNA” /db_xref=“FlyBase:FBgn ” gene /note=“decapentaplegic” /gene=“dpp” /allele=“” /db_xref=“FlyBase:FBgn ” CDS /gene=“dpp” /note=“decapentaplegic protein (1188 could be 1587)” /codon_start=1 /db_xref=“FlyBase:FBgn ” /db_xref=“PID:g157292” /translation=“MRAWLLLLAVLATFQTIVRVASTEDISQRFIAAIAPVAAHIPLA SASGSGSGRSGSRSVGASTSTALAKAFNPFSEPASFSDSDKSHRSKTNKKPSKSDANR …………………… LGYDAYYCHGKCPFPLADHFNSTNAVVQTLVNNMNPGKVPKACCVPTQLDSVAMLYL NDQSTBVVLKNYQEMTBBGCGCR” BASE COUNT1170 a1078 c956 g797 t ORIGIN 1 gtcgttcaac agcgctgatc gagtttaaat ctataccgaa atgagcggcg gaaagtgagc 61 cacttggcgt gaacccaaag ctttcgagga aaattctcgg acccccatat acaaatatcg 121 gaaaaagtat cgaacagttt cgcgacgcga agcgttaaga tcgcccaaag atctccgtgc 181 ggaaacaaag aaattgaggc actattaaga gattgttgtt gtgcgcgagt gtgtgtcttc 241 agctgggtgt gtggaatgtc aactgacggg ttgtaaaggg aaaccctgaa atccgaacgg 301 ccagccaaag caaataaagc tgtgaatacg aattaagtac aacaaacagt tactgaaaca 361 gatacagatt cggattcgaa tagagaaaca gatactggag atgcccccag aaacaattca 421 attgcaaata tagtgcgttg cgcgagtgcc agtggaaaaa tatgtggatt acctgcgaac 481 cgtccgccca aggagccgcc gggtgacagg tgtatccccc aggataccaa cccgagccca 541 gaccgagatc cacatccaga tcccgaccgc agggtgccag tgtgtcatgt gccgcggcat 601 accgaccgca gccacatcta ccgaccaggt gcgcctcgaa tgcggcaaca caattttcaa ………………………… aactgtataa acaaaacgta tgccctataa atatatgaat aactatctac atcgttatgc 3901 gttctaagct aagctcgaat aaatccgtac acgttaatta atctagaatc gtaagaccta 3961 acgcgtaagc tcagcatgtt ggataaatta atagaaacga g //

Example of sequence database entry for SWISS-PROT IDDECA_DROMESTANDARD;PRT;588AA. ACP07713; DT01-APR-1988 (REL. 07, CREATED) DT01-APR-1988 (REL. 07, LAST SEQUENCE UPDATE) DT01-FEB-1995 (REL. 31, LAST ANNOTATION UPDATE) DEDECAPENTAPLEGIC PROTEIN PRECURSOR (DPP-C PROTEIN). GNDPP. OSDROSOPHILA MELANOGASTER (FRUIT FLY). OCEUKARYOTA; METAZOA; ARTHROPODA; INSECTA; DIPTERA. RN[1] RPSEQUENCE FROM N.A. RM RAPADGETT R.W., ST JOHNSTON R.D., GELBART W.M.; RLNATURE 325:81-84 (1987) RN[2] RPCHARACTERIZATION, AND SEQUENCE OF RM RAPANGANIBAN G.E.F., RASHKA K.E., NEITZEL M.D., HOFFMANN F.M.; RLMOL. CELL. BIOL. 10: (1990). CC-!- FUNCTION: DPP IS REQUIRED FOR THE PROPER DEVELOPMENT OF THE CC EMBRYONIC DOORSAL HYPODERM, FOR VIABILITY OF LARVAE AND FOR CELL CC VIABILITY OF THE EPITHELIAL CELLS IN THE IMAGINAL DISKS. CC-!- SUBUNIT: HOMODIMER, DISULFIDE-LINKED. CC-!- SIMILARITY: TO OTHER GROWTH FACTORS OF THE TGF-BETA FAMILY. DREMBL; M30116; DMDPPC. DRPIR; A26158; A DRHSSP; P08112; 1TFG. DRFLYBASE; FBGN ; DPP. DRPROSITE; PS00250; TGF_BETA. KWGROWTH FACTOR; DIFFERENTIATION; SIGNAL. FTSIGNAL1?POTENTIAL. FTPROPEP?456 FTCHAIN457588DECAPENTAPLEGIC PROTEIN. FTDISULFID487553BY SIMILARITY. FTDISULFID516585BY SIMILARITY. FTDISULFID520587BY SIMILARITY. FTDISULFID552552INTERCHAIN (BY SIMILARITY). FTCARBOHYD120120POTENTIAL. FTCARBOHYD342342POTENTIAL. FTCARBOHYD377377POTENTIAL. FTCARBOHYD529529POTENTIAL. SQSEQUENCE 588 AA; 65850MW; CN; MRAWLLLLAV LATFQTIVRV ASTEDISQRF IAAIAPVAAH IPLASASGSG SGRSGSRSVG ASTSTAGAKA FNRFSEPASF SDSDKSHRSK TNKKPSKSDA NRQFNEVHKP RTDQLENSKN KSKQLVNKPN HNKMAVKEQR SHHKKSHHHR SHQPKQASAS TESHQSSSIE SIFVEEPTLV LDREVASINV PANAKAIIAE QGPSTYSKEA LIKDKLKPDP STYLVEIKSL LSLFNMKRPP KIDRSKIIIP EPMKKLYAEI MGHELDSVNI PKPGLLTKSA NTVRSFTHKD SKIDDRFPHH HRFRLHFDVK SIPADEKLKA AELQLTRDAL SQQVVASRSS ANRTRYQBLV YDITRVGVRG QREPSYLLLD TKTBRLNSTD TVSLDVQPAV DRWLASPQRN YGLLVEVRTV RSLKPAPHHH VRLRRSADEA HERWQHKQPL LFTYTDDGRH DARSIRDVSG GEGGGKGGRN KRHARRPTRR KNHDDTCRRH SLYVDFSDVG WDDWIVAPLG YDAYYCHGKC PFPLADHRNS TNHAVVQTLV NNMNPGKBPK ACCBPTQLDS VAMLYLNDQS TVVLKNYQEM TVVGCGCR

Functional classification of E. coli genes according to Monica Riley

The Protein Folding Problem

Protein Folding Problem (Sequence 3D Structure) 1 Protein folding is thermodynamically determined (Anfinsen’s thermodynamic principle ) Protein + Environment 2. Protein folding is a reaction imvolving other interacting molecules (Principle of molecular interactions) Protein + Chaperonins +….

Central Paradigm

Bioinformatics : A Long Journey (How far are we away from knowing the God ??) Sequence to exon 80% [Laub 98] Exons to gene (without cDNA or homolog) ~30% [Laub 98] Gene to regulation ~10% [Hughes 00] Regulated gene to protein sequence 98% [Gesteland ] Sequence to secondary-structure ( , ,c) 77% [CASP] Secondary-structure to 3D structure 25% [CASP] 3D structure to ligand specificity ~10% [Johnson 99] Expected accuracy overall ~ = 0.8*.3*.1*.98*.77*.25*.1 =.0005 ?

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