Coexistence of Native and Denatured Phases in a Single Proteinlike Molecule

In order to understand the nuclei which develop during the course of protein folding and unfolding, we examine equilibrium coexistence of phases within a single heteropolymer chain. We computationally generate the phase segregation by applying a “folding pressure,” or adding an energetic bonus for native monomer-monomer contacts. The computer models reveal that in a polymer system some nuclei hinder folding via topological constraints. Using this insight, we show that the critical nucleus size is of the order of the entire chain and that unfolding time scales as $\exp \left({\mathrm{cN}}^{2/3}\right)$, in the large $N$ limit, $N$ and $c$ being the chain length and a constant, respectively.