Osmolyte-induced conformational stabilization of a hydrophobic polymer

Abstract

Elucidating the mechanistic role of osmolytes on conformations of hydrophobic prototypical macromolecules in principle is the stepping stone towards understanding the effect of osmolytes on proteins. Motivated by this, we use equilibrium simulations and umbrella sampling techniques to dissect the underlying mechanism of osmolyte-induced conformational stability of a hydrophobic polymer. Our results unveil a remarkable osmolyte-dependent conformational stabilization of the polymer. In an aqueous solution of 4 M choline chloride (ChCl), the polymer has an even more compact structure than in water. On the other hand, an aqueous solution of 8 M urea stabilizes the extended state of the polymer. Interestingly, the polymer adopts an intermediate hairpin conformation in a mixed osmolyte solution of 4 M ChCl and 8 M urea in water due to the interplay of ChCl and urea. Our simulations identify the relative accumulation of water and the hydrophilic part of choline or preferential binding of urea near the collapsed and the extended states, respectively. Analyses split out the enthalpic and entropic contributions to the overall free energy. This decides the stabilization of the preferred conformation in the chosen osmolyte solution. Our simulations show that in an aqueous solution of ChCl, the hairpin state is stabilized by entropy gain. In contrast, the enthalpic contribution stabilizes the hairpin state in mixed environments. However, a collapsed state is energetically not favored in the presence of urea. In brief, via employing an in silico approach, the current findings indicate the importance of osmolytes in stabilizing the conformational states of hydrophobic polymers.