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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
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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
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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
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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