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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 revisited
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Double helix
A, C, G, T “letters”
A::T = 1
G::C = 1
Image from http://en.wikipedia.org/wiki/DNA
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
CSCI 4314/5314, Algorithms for Molecular Biology
Base pairs bond to give double helix
Image from http://en.wikipedia.org/wiki/DNA
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
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
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
CSCI 4314/5314, Algorithms for Molecular Biology
DNA transcription to RNA
Image from http://en.wikipedia.org/wiki/Transcription_%28genetics%29
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)
CSCI 4314/5314, Algorithms for Molecular Biology
RNA splicing can give many variants
Image from http://en.wikipedia.org/wiki/Alternative_splicing
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RNA 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
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
CSCI 4314/5314, Algorithms for Molecular Biology
Ribosomes at work
Image from http://cellbio.utmb.edu/cellbio/ribosome.htm
CSCI 4314/5314, Algorithms for Molecular Biology
Overview: transcription/translation
Image from http://en.wikipedia.org/wiki/MRNA
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
Structural proteins
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
RNA
• 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
• 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