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COT 6930 HPC and Bioinformatics Introduction to Molecular Biology. Xingquan Zhu Dept. of Computer Science and Engineering. Outline. Cell DNA DNA Structure DNA Sequencing RNA (DNA-> RNA) Protein Protein structure Protein synthesis. Replication. Transcription. Translation.
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COT 6930HPC and BioinformaticsIntroduction to Molecular Biology Xingquan Zhu Dept. of Computer Science and Engineering
Outline • Cell • DNA • DNA Structure • DNA Sequencing • RNA (DNA-> RNA) • Protein • Protein structure • Protein synthesis
Replication Transcription Translation Central Dogma of Biology: DNA, RNA, and the Flow of Information
Lys Lys Gly Gly Leu Val Ala His Cartoon Space filling Oxygen Nitrogen Carbon Sulfur Ribbon Surface Protein • A sequence from 20 amino acids • Adopts a stable 3D structure that can be measured experimentally
The 20 amino acids • Each amino acid contains an "amine" group (NH3) and a "carboxy" group (COOH) (shown in black in the diagram). • The amino acids vary in their side chains (indicated in blue in the diagram).
Protein Structure • Protein Structure • Primary structure (amino acid sequence) • Secondary structure (local folding) • Tertiary Structure (global folding) • Quaternary structure (multiple-chain) • Protein Structure Animation • https://mywebspace.wisc.edu/jonovic/web/proteins.html
Primary Structure • Primary structure is described by the sequence of Amino Acids in the chain
Polypeptide N-terminal C- terminal One end of every polypeptide, called the amino terminal or N-terminal, has a free amino group. The other end, with its free carboxyl group, is called the carboxyl terminal or C-terminal. Peptide: 50 amino acids or less Polypeptide: 50-100 amino acids Protein: over 100 amino acids
Polypeptide • The amino acids are linked covalently by peptide bonds. The image shows how three amino acids linked by peptide bonds into a tripeptide.
Secondary Structure • Secondary structure describes the way the chain folds • Local structure of consecutive amino acids • Common regular secondary structures • Helix • Sheet • b turn
Secondary Structure • Alpha helix • Beta strand / pleated sheet • Coil
Tertiary Structure of protein • Tertiary Structure describes the shapes which form when the secondary spirals of the protein chain further fold up on themselves.
Quaternary structure (multi-chain structures) • Quaternary structure describes any final adjustments to the molecule before it can become active. For example, pairs of chains may bind together or other inorganic substances may be incorporated into the molecule.
Protein Structure Space Protein folding taxonomy : all alphaall betaalpha/betaalpha+betaothers http://www.nigms.nih.gov/psi/
rotatable rotatable Geometry of Protein Structure Total number of degree is 2*(n-1) where n is the length of the protein
The Leventhal Paradox • Given a small protein (100aa) assume 3 possible conformations/peptide bond • 3100 = 5 × 1047 conformations • Fastest motions 10- 15 sec so sampling all conformations would take 5 × 1032 sec • 60 × 60 × 24 × 365 = 31536000 seconds in a year • Sampling all conformations will take 1.6 × 1025 years • Proteins do not have problem in folding, we have! the Leventhal paradox
Outline • Cell • DNA • DNA Structure • DNA Sequencing • RNA (DNA-> RNA) • Protein • Protein structure • Protein synthesis
RNA 3 types of RNA
Messenger RNA DNA: TAC CAT GAG ACT … ATC mRNA: AUG GUA CUC UGA … UAG
Overview of protein synthesis Transcription: same language Translation: different language
A. Transcription No Thymine, instead has Uracil
Rules (the secret of life) • G →C • C →G • Transcription: • A →U • T →A • Translation AUG: Methionine (Met)
Codons and anticodons DNA: TAC CAT GAG ACT … ATC mRNA: AUG GUA CUC UGA … UAG tRNA: UAC CAU GAG ACU … AUC
Protein structure databases Gene expression database transcription translation DNA RNA protein phenotype Protein sequence databases cDNA ESTs UniGene Genomic DNA Databases
Transcription & Open Reading Frame (ORF) • Open Reading Frame (ORF) • Where to start reading codons (ATG) • 6 possible reading frames (3 forward, 3 backward) • Gene is usually longest ORF found • Forward reading frame example
Complication – Non-coding Regions • Non-coding regions • Very little genomic DNA produce proteins • Exon – DNA expressed in protein (2–3% of human genome) • Intron – DNA transcribed into mRNA but later removed • Untranslated region (UTR) – DNA not expressed • UTRs may affect gene regulation & expression • Biological processes • Remove introns from mRNA, splice exons together • Transition between intron / exon = splice site • Splicing can be inconsistent • Some exons may be skipped • Result = splice-variant gene / isoform • Estimated 30% of human proteins from splice-variant genes
Control regions Exons Transcription Introns Splicing Transcription • The process of making RNA from DNA • Needs a promoter region to begin transcription.
Alternative Splicing • One single gene produce different forms of a protein • A single gene can contain numerous exons and introns, and the exons can be spliced together in different ways
Complication: Mutations • Mutations • Modifications during DNA replication • Possible changes • Point mutation / single nucleotide polymorphism (SNP) • 5’ A T A C G T A … • 5’ A T G C G T A … • Occur every 100 to 300 bases along the 3-billion-base human genome • Duplicate sequence • Inverted sequence • Insert / delete sequence ( indel )
Outline • Cell • DNA • DNA Structure • DNA Sequencing • RNA (DNA-> RNA) • Protein • Protein structure • Protein synthesis
Excellent Animation • Cell • http://www.youtube.com/watch?v=UB6G9GD2KFk • Central Dogma • http://www.youtube.com/watch?v=GkdRdik73kU