Statistical Mechanics of Helix Bundles Using a Dynamic
Programming Approach
Adam Lucas
Liang Huang
Aravind Joshi
Ken A. Dill
10.1021/ja067153s.s001
https://acs.figshare.com/articles/journal_contribution/Statistical_Mechanics_of_Helix_Bundles_Using_a_Dynamic_Programming_Approach/3013540
Despite much study, biomolecule folding cooperativity is not well understood. There are
quantitative models for helix-coil transitions and for coil-to-globule transitions, but no accurate models yet
treat both chain collapse and secondary structure formation together. We develop here a dynamic
programming approach to statistical mechanical partition functions of foldamer chain molecules. We call it
the ascending levels model. We apply it to helix-coil and helix-bundle folding and cooperativity. For 14- to
50-mer Baldwin peptides, the model gives good predictions for the heat capacity and helicity versus
temperature and urea. The model also gives good fits for the denaturation of Oas's three-helix bundle B
domain of protein A (F13W*) and synthetic protein α<sub>3</sub><i>C</i> by temperature and guanidine. The model predicts
the conformational distributions. It shows that these proteins fold with transitions that are two-state, although
the transitions in the Baldwin helices are nearly higher order. The model shows that the recently developed
three-helix bundle polypeptoids of Lee et al. fold <i>anti-cooperatively</i>, with a predicted value of Δ<i>H</i><sub>vH</sub>/Δ<i>H</i><sub>cal</sub> =
0.72. The model also predicts that two-helix bundles are unstable in proteins but stable in peptoids. Our
dynamic programming approach provides a general way to explore cooperativity in complex foldable
polymers.
2007-04-11 00:00:00
13W
foldamer chain molecules
protein α3 C
transition
Dynamic Programming ApproachDespite
cooperativity
bundle
programming approach
model