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An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Algorithms for Molecular Biology CSCI 4314-001 Elizabeth White [email protected] CSCI 4314/5314, Algorithms for Molecular Biology DNA, RNA are similar Image from http://en.wikipedia.org/wiki/RNA_world_hypothesis CSCI 4314/5314, Algorithms for Molecular Biology 4 kinds of RNA in the cell • Messenger RNA (mRNA) • Always ends up being translated into protein • Function: information storage • Small nuclear RNA (snRNA) • Never translated, just stays around as RNA • Function: machinery for mRNA splicing • Transfer RNA (tRNA), ribosomal RNA (rRNA) • Never translated, just stays around as RNA • Function: machinery for reading mRNA into protein CSCI 4314/5314, Algorithms for Molecular Biology mRNA specifies 3-base codons Image from http://en.wikipedia.org/wiki/Genetic_code CSCI 4314/5314, Algorithms for Molecular Biology 3-letter codons map to amino acids Image from http://www.pangloss.com/seidel/Protocols/codon.html CSCI 4314/5314, Algorithms for Molecular Biology Transfer RNAs do the mapping Image from http://cropandsoil.oregonstate.edu/classes/css430/lecture%209-07/figure-09-10.JPG CSCI 4314/5314, Algorithms for Molecular Biology Ribosomes do the work of connecting amino acids into a protein Image from http://www.modares.ac.ir/elearning/Dalimi/Proto/Lectures/week2/week2.htm CSCI 4314/5314, Algorithms for Molecular Biology Ribosomes are mostly RNA (orange) with some protein decorations (blue) Image from http://www.modares.ac.ir/elearning/Dalimi/Proto/Lectures/week2/week2.htm CSCI 4314/5314, Algorithms for Molecular Biology Translation proceeds via ribosome Image from http://www.scripps.edu/chem/wong/rna.html CSCI 4314/5314, Algorithms for Molecular Biology Overview: transcription/translation Image from http://www.cbs.dtu.dk/staff/dave/DNA_CenDog.html CSCI 4314/5314, Algorithms for Molecular Biology Protein structure • Primary: amino acid sequence • Secondary: short regions of protein form • Alpha-helix • Beta-sheet • Tertiary: helices and sheets nestle together to make a 3 dimensional shape • Quaternary: 2 or more proteins associate together CSCI 4314/5314, Algorithms for Molecular Biology Primary structure: amino acid sequence Top image from http://en.wikipedia.org/wiki/Amino_acid Bottom image from http://commons.wikimedia.org/wiki/Image:2-amino-acids.png CSCI 4314/5314, Algorithms for Molecular Biology Secondary structure: alpha-helix Left image from http://commons.wikimedia.org/wiki/Image:AlphaHelixProtein_fr.jpg Bottom image from http://www.srs.ac.uk/px/showcase/guide_files/helix4.jpg CSCI 4314/5314, Algorithms for Molecular Biology Secondary structure: beta-sheet Left image from http://www.sciencecollege.co.uk/SC/biochemicals.html Right image from http://cnx.org/content/m11614/latest/ CSCI 4314/5314, Algorithms for Molecular Biology Tertiary structure: 3D shape Image from http://www.colorado.edu/chem/people/wuttked.html CSCI 4314/5314, Algorithms for Molecular Biology Quaternary structure: assembly Image from http://www.man.poznan.pl/CBB/GIF/hcc-beta.jpg CSCI 4314/5314, Algorithms for Molecular Biology Some proteins just hold stuff together Image from http://www.wellesley.edu/Chemistry/chem227/structproteins/strctprt.htm CSCI 4314/5314, Algorithms for Molecular Biology DNA-binding proteins • Recognize particular DNA sequences • Regulate which genes are transcribed into mRNA • Often act in pairs Image from http://en.wikipedia.org/wiki/DNA CSCI 4314/5314, Algorithms for Molecular Biology Enzymatic proteins • Catalyze chemical reactions • Beta-lactamase enzyme inactivates penicillin Image from http://www.nersc.gov/news/annual_reports/annrep97/bash.html CSCI 4314/5314, Algorithms for Molecular Biology Open problem: protein folding • Amino acid sequence of protein determines its shape • In theory, we should be able to deduce a protein’s shape from its sequence • “Holy Grail” question for biology • Open door to “designer” proteins • Allow for faster, cheaper biomedical research CSCI 4314/5314, Algorithms for Molecular Biology Protein backbone is free to rotate Each amino acid residue in the protein can spin around phi, psi angles (but not omega) CSCI 4314/5314, Algorithms for Molecular Biology In practice? Too many choices • Levinthal paradox • Consider a 100-amino acid protein (not big) • Suppose there are 3 choices for each phi, psi angle • This means that 3200 conformations are possible • Can a protein try each one randomly? • Suppose it can test one conformation in 10-15 sec • Will take about 1080 seconds to test all • Note: the universe is about 1020 seconds old • In nature, proteins fold in seconds (or less). • Conclusion: folding is NOT a random search