How Macromolecular Solvation Influences Its Conformations

Under ambient conditions, globular proteins sacrifice their conformational entropy, and fold into well-defined “native” states. They do so because folding leads to favorable intra-molecular interactions, and importantly, to more favorable (or less unfavorable) interactions with the solvent. Consequently, proteins can be denatured under a variety of conditions, by either making the folded protein-solvent interactions less favorable, or unfolded protein-solvent interactions more favorable. Such conditions include lower temperatures, higher pressures, proximity to hydrophobic interfaces, and the presence of co-solutes that act as denaturants. Using hydrophobic polymers as model globular proteins, here we study how the hydration environment of a polymer influences its collapse. We find that near ambient conditions, typical hydrophobic macromolecules are situated at the edge of a collective collapse transition, making them sensitive to perturbations such as the application of pressure or the presence of co-solutes.