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 revisited Double helix A, C, G, T “letters” A::T = 1 G::C = 1 Image from http://en.wikipedia.org/wiki/DNA

3. CSCI 4314/5314, Algorithms for Molecular Biology Why these ratios? Same size pairs Matching shapes Matching charges Image from http://en.wikipedia.org/wiki/DNA

4. CSCI 4314/5314, Algorithms for Molecular Biology Base pairs bond to give double helix Image from http://en.wikipedia.org/wiki/DNA

5. CSCI 4314/5314, Algorithms for Molecular Biology DNA is designed to be replicated Each of the 2 strands can specify the other one Result is 2 helices, each with one old strand and one new Image from http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookDNAMOLGEN.html

6. CSCI 4314/5314, Algorithms for Molecular Biology Replication bubbles (made of 2 forks) Image from http://www.mun.ca/biochem/courses/3107/images/lambda_0017a.jpg

7. CSCI 4314/5314, Algorithms for Molecular Biology DNA is designed to be transcribed Similar mechanism to replication Result is original helix + RNA strand Image from http://www.bioedonline.org/slides/slide01.cfm?q=%22transcription%22&dpg=11

8. CSCI 4314/5314, Algorithms for Molecular Biology DNA transcription to RNA Image from http://en.wikipedia.org/wiki/Transcription_%28genetics%29

9. CSCI 4314/5314, Algorithms for Molecular Biology RNA molecule is processed further Except in bacteria, RNA molecule contains Introns: do not code for protein Exons: protein-coding regions Introns are spliced out of the RNA transcript Result is “messenger RNA”, mRNA Image from http://en.wikipedia.org/wiki/Splicing_(genetics)

10. CSCI 4314/5314, Algorithms for Molecular Biology RNA splicing can give many variants Image from http://en.wikipedia.org/wiki/Alternative_splicing

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

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

13. 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

14. CSCI 4314/5314, Algorithms for Molecular Biology Translation: RNA to protein Messenger RNA is “read” by a ribosome Ribosome connects amino acids to build new protein strand as it reads Image from http://www.bioedonline.org/slides/slide01.cfm?q=translation&dpg=8

15. CSCI 4314/5314, Algorithms for Molecular Biology Ribosomes at work Image from http://cellbio.utmb.edu/cellbio/ribosome.htm

16. CSCI 4314/5314, Algorithms for Molecular Biology Overview: transcription/translation Image from http://en.wikipedia.org/wiki/MRNA

17. 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

18. 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

19. 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

20. 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/

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

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

23. CSCI 4314/5314, Algorithms for Molecular Biology Structural proteins Image from http://www.wellesley.edu/Chemistry/chem227/structproteins/strctprt.htm

24. CSCI 4314/5314, Algorithms for Molecular Biology DNA-binding proteins Recognize particular DNA sequences Regulate which genes are transcribed into RNA Often act in pairs Image from http://en.wikipedia.org/wiki/DNA

25. 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

26. CSCI 4314/5314, Algorithms for Molecular Biology Open problem: protein folding Amino acid sequence of protein determines its shape Proteins seem to “fall” into correct shape In theory, we should be able to look at a protein’s sequence and deduce its shape Unfortunately, this is not computationally possible In practice, we deduce shapes by similarity Proteins with similar amino acid sequences tend to take similar shapes