title: Statistical mechanics of helix bundles using a dynamic programming approach.
abstract: 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 alpha3C 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 anti-cooperatively, with a predicted value of DeltaHvH/DeltaHcal = 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.
authors.affiliation: Department of Mathematics, Saint Mary's College of California, Moraga, California 94575-3517, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Lucas
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.forename: Aravind
authors.initials: A
authors.lastname: Joshi
authors.forename: Ken A
authors.initials: KA
authors.lastname: Dill
mesh_terms: D002151:Calorimetry; D003198:Computer Simulation; D008958:Models, Molecular; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature; D013816:Thermodynamics
chemical_list: D011506:Proteins