Atoosimplemodelforproteinfolding.ppt

A too simple model forprotein folding Ethan Bolker Mathematics and Computer Science UMass Boston Clark University April 14, 2004 Preliminaries Problem source: biology teaching need, Analysis mixes biology, cs, mathematics (= applied mathematics) Ongoing help from Bogdan Calota See /~eb/folding How life works DNA (gene) makes RNA RNA makes polypeptide Polypeptide folds into protein Proteins interact (biochemistry) Cells … organisms … communities … Natural selection makes gene mix evolve Virtual teaching laboratories For Brian White (Biology, UMass Boston) Virtual Genetics Laboratory (VGL) Mendelian genetics /VGL/index.htm Science, April 16, 2004 GenExplorer the central dogma /genex/ Watch this space … Polypeptide ? protein Polypeptide: sequence of amino acids chemical (biological) activity depends on three dimensional configuration (folding) Protein: polypeptide folded into active shape Given the sequence, what’s the shape? Wet lab lots of chemistry x-ray crystallography (newer tools) Virtual lab compute shape from chemical principles need supercomputer or grid folding@home /group/pandegroup/folding/ For beginning biologists Problem: give students hands on experience showing how sequence determines shape Solution: very simple model amino acid = disk in the plane, hydrophobic index hi expresses wish to avoid wet environment fold polypeptide on hex grid to minimize energy energy = Σ (# exposed edges) ? hi acids folding@umb folding@umb Brute force search Try all nonintersecting walks of length n on plane grid of hexagons: 1, 6, 30, 138, 618, 2730, 11946, 51882, 224130, 964134, 4133166, … Sequence # A001334 in the Online Encyclopedia of Integer Sequences /~njas/sequences/ No closed form expression Growth rate obviously O(5n), actual ? 4.25n To count foldings, divide by 12 (symmetry) A (random) chain of length 17 Open questions (statistical) How many minima