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www.bioalgorithms.infoAn Introduction to Bioinformatics Algorithms
Algorithms for Molecular Biology
CSCI 4314-001
Elizabeth White
elizabeth.white@colorado.edu
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_acidBottom image from http://commons.wikimedia.org/wiki/Image:2-amino-acids.png
CSCI 4314/5314, Algorithms for Molecular Biology
Left image from http://commons.wikimedia.org/wiki/Image:AlphaHelixProtein_fr.jpgBottom image from http://www.srs.ac.uk/px/showcase/guide_files/helix4.jpg
Secondary structure: alpha-helix
CSCI 4314/5314, Algorithms for Molecular Biology
Secondary structure: beta-sheet
Left image from http://www.sciencecollege.co.uk/SC/biochemicals.htmlRight 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 rotateEach 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
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