Abstract
| - Despite much study, biomolecule folding cooperativity is not well understood. There arequantitative models for helix-coil transitions and for coil-to-globule transitions, but no accurate models yettreat both chain collapse and secondary structure formation together. We develop here a dynamicprogramming approach to statistical mechanical partition functions of foldamer chain molecules. We call itthe ascending levels model. We apply it to helix-coil and helix-bundle folding and cooperativity. For 14- to50-mer Baldwin peptides, the model gives good predictions for the heat capacity and helicity versustemperature and urea. The model also gives good fits for the denaturation of Oas's three-helix bundle Bdomain of protein A (F13W*) and synthetic protein α3C by temperature and guanidine. The model predictsthe conformational distributions. It shows that these proteins fold with transitions that are two-state, althoughthe transitions in the Baldwin helices are nearly higher order. The model shows that the recently developedthree-helix bundle polypeptoids of Lee et al. fold anti-cooperatively, with a predicted value of ΔHvH/ΔHcal =0.72. The model also predicts that two-helix bundles are unstable in proteins but stable in peptoids. Ourdynamic programming approach provides a general way to explore cooperativity in complex foldablepolymers.
|