1. www.bioalgorithms.infoAn Introduction to Bioinformatics Algorithms Algorithms for Molecular Biology CSCI 4314-001 Elizabeth White elizabeth.white@colorado.edu

2. CSCI 4314/5314, Algorithms for Molecular Biology DNA, RNA are similar Image from http://en.wikipedia.org/wiki/RNA_world_hypothesis

3. 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

4. CSCI 4314/5314, Algorithms for Molecular Biology mRNA specifies 3-base codons Image from http://en.wikipedia.org/wiki/Genetic_code

5. CSCI 4314/5314, Algorithms for Molecular Biology 3-letter codons map to amino acids Image from http://www.pangloss.com/seidel/Protocols/codon.html

6. 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

7. 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

8. 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

9. CSCI 4314/5314, Algorithms for Molecular Biology Translation proceeds via ribosome Image from http://www.scripps.edu/chem/wong/rna.html

10. CSCI 4314/5314, Algorithms for Molecular Biology Overview: transcription/translation Image from http://www.cbs.dtu.dk/staff/dave/DNA_CenDog.html

11. 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

12. 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

13. CSCI 4314/5314, Algorithms for Molecular Biology 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 Secondary structure: alpha-helix

14. CSCI 4314/5314, Algorithms for Molecular Biology Secondary structure: beta-sheet Left image from http://www.sciencecollege.co.uk/SC/biochemicals.htmlhttp://www.sciencecollege.co.uk/SC/biochemicals.html Right image from http://cnx.org/content/m11614/latest/

15. CSCI 4314/5314, Algorithms for Molecular Biology Tertiary structure: 3D shape Image from http://www.colorado.edu/chem/people/wuttked.html

16. CSCI 4314/5314, Algorithms for Molecular Biology Quaternary structure: assembly Image from http://www.man.poznan.pl/CBB/GIF/hcc-beta.jpg

17. CSCI 4314/5314, Algorithms for Molecular Biology Some proteins just hold stuff together Image from http://www.wellesley.edu/Chemistry/chem227/structproteins/strctprt.htm

18. 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

19. 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

20. 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

21. 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)

22. 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 3 200 conformations are possible Can a protein try each one randomly? Suppose it can test one conformation in 10 -15 sec Will take about 10 80 seconds to test all Note: the universe is about 10 20 seconds old In nature, proteins fold in seconds (or less). Conclusion: folding is NOT a random search