Why Don't Some Strongly Attracting Heteropolymers Phase Separate?

A puzzling question in polymer science is why some heteropolymers that exhibit strongly attractive pairwise interactions do not undergo phase separation. Unlike simple liquids and colloidal suspensions, where the second virial coefficient can unambiguously predict whether phase separation occurs, this is not always the case for heteropolymer solutions. To investigate the sequence-dependent relationship between pairwise polymer interactions and phase behavior, we describe a simulation study of model heteropolymers that have identical second virial coefficients but divergent phase behaviors. By examining the potential of mean force and contact maps derived from the conformations of interacting polymer pairs, we are able to identify mechanistic factors responsible for their disparate phase behaviors. Our analysis establishes a computational tool for predicting heteropolymer phase behavior based solely on pairwise polymer interactions and their associated contact maps, and also advances our mechanistic understanding of the phase behavior of complex biopolymer systems.