Introduction to Bioinformatics Algorithms Algorithms for Molecular Biology CSCI Elizabeth White

CSCI 4314/5314, Algorithms for Molecular Biology DNA, RNA are similar Image from

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

CSCI 4314/5314, Algorithms for Molecular Biology 3-letter codons map to amino acids Image from

CSCI 4314/5314, Algorithms for Molecular Biology Transfer RNAs do the mapping Image from

CSCI 4314/5314, Algorithms for Molecular Biology Ribosomes do the work of connecting amino acids into a protein Image from

CSCI 4314/5314, Algorithms for Molecular Biology Ribosomes are mostly RNA (orange) with some protein decorations (blue) Image from

CSCI 4314/5314, Algorithms for Molecular Biology Translation proceeds via ribosome Image from

CSCI 4314/5314, Algorithms for Molecular Biology Overview: transcription/translation Image from

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 Bottom image from

CSCI 4314/5314, Algorithms for Molecular Biology Left image from Bottom image from Secondary structure: alpha-helix

CSCI 4314/5314, Algorithms for Molecular Biology Secondary structure: beta-sheet Left image from Right image from

CSCI 4314/5314, Algorithms for Molecular Biology Tertiary structure: 3D shape Image from

CSCI 4314/5314, Algorithms for Molecular Biology Quaternary structure: assembly Image from

CSCI 4314/5314, Algorithms for Molecular Biology Some proteins just hold stuff together Image from

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

CSCI 4314/5314, Algorithms for Molecular Biology Enzymatic proteins Catalyze chemical reactions Beta-lactamase enzyme inactivates penicillin Image from

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 conformations are possible Can a protein try each one randomly? Suppose it can test one conformation in sec Will take about seconds to test all Note: the universe is about seconds old In nature, proteins fold in seconds (or less). Conclusion: folding is NOT a random search