Ethanol Effects on the Folding-Unfolding of Hydrophobic Polymers

Hydrophobic interactions play an important role in biological self-assembly processes, such as protein folding, micelle and membrane formation, and molecular recognition. Several experimental, theoretical, and simulation studies have focused on the effects of ethanol on protein stability. They imply weakening of protein stability and hydrophobic interactions with increasing concentration of ethanol. To understand the molecular origins of effects of alcohols on hydrophobic interactions at small and large lengthscales, we studied folding-unfolding behavior of model hydrophobic polymers in pure water, pure ethanol, and in water-ethanol mixtures [40% (v/v)]. We focused on thermodynamic as well as structural aspects of the process. We find that effects of ethanol addition are non-monotonic. A small addition of ethanol actually stabilizes hydrophobic interactions, which weaken with increasing ethanol concentration. Structural analysis of ethanol-water mixtures indicate that these mixtures, although miscible macroscopically, are nanoscopically phase separated. The hydrophobic molecules (such as the polymers studied here) partition favorably in ethanol rich nanophases. Ethanol coates the surface of the polymer and stabilizes it at smaller concentrations and destabilizes it at higher concentrations. Despite significant useful insights obtained from those studies, a detailed molecular level understanding of the phenomena still remains incomplete. Further studies at higher concentration of ethanol are in progress.