www.bioalgorithms.infoan introduction to bioinformatics algorithms algorithms for molecular biology...

www.bioalgorithms.infoAn Introduction to Bioinformatics Algorithms

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


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


mRNA specifies 3-base codons

Image from http://en.wikipedia.org/wiki/Genetic_code


3-letter codons map to amino acids

Image from http://www.pangloss.com/seidel/Protocols/codon.html


Transfer RNAs do the mapping

Image from http://cropandsoil.oregonstate.edu/classes/css430/lecture%209-07/figure-09-10.JPG


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


Ribosomes are mostly RNA (orange) with some protein decorations (blue)

Image from http://www.modares.ac.ir/elearning/Dalimi/Proto/Lectures/week2/week2.htm


Translation proceeds via ribosome

Image from http://www.scripps.edu/chem/wong/rna.html


Overview: transcription/translation

Image from http://www.cbs.dtu.dk/staff/dave/DNA_CenDog.html


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


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


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


Secondary structure: beta-sheet

Left image from http://www.sciencecollege.co.uk/SC/biochemicals.htmlRight image from http://cnx.org/content/m11614/latest/


Tertiary structure: 3D shape

Image from http://www.colorado.edu/chem/people/wuttked.html


Quaternary structure: assembly

Image from http://www.man.poznan.pl/CBB/GIF/hcc-beta.jpg


Some proteins just hold stuff together

Image from http://www.wellesley.edu/Chemistry/chem227/structproteins/strctprt.htm


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


Enzymatic proteins• Catalyze chemical reactions

• Beta-lactamase enzyme inactivates penicillin

Image from http://www.nersc.gov/news/annual_reports/annrep97/bash.html


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


Protein backbone is free to rotateEach amino acid residue in the protein can spin

around phi, psi angles (but not omega)


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

www.bioalgorithms.infoan introduction to bioinformatics algorithms algorithms for molecular biology...

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