Solvation versus freezing in a heteropolymer globule

We address the response of a random heteropolymer to preferential solvation of certain monomer types at the globule-solvent interface. For each set of monomers that can comprise the molecule’s surface, we represent the ensemble of allowed configurations by a Gaussian distribution of energy levels, whose mean and variance depend on the set’s composition. Within such a random energy model, mean surface composition is proportional to solvation strength under most conditions. The breadth of this linear response regime arises from the approximate statistical independence of surface and volume energies. Fluctuations play a crucial role in determining the excess of solvophilic monomers at the surface, and for a diverse set of monomer types can be overcome only by very strong solvent preference.