Unveiling the Effect of Choline Chloride on Hydrophobic Association of Methane

Abstract

Elucidating how osmolytes influence hydrophobic interactions in small nonpolar solutes helps to explain their role in biology. This is crucial for understanding protein stability, enzyme-substrate binding, and membrane self-assembly. Motivated by this, we employ equilibrium simulations and umbrella sampling to explore the molecular basis of the osmolyte-induced association of methane molecules. Our study reveals a remarkable enhancement in methane association driven by choline chloride (ChCl). Radial distribution functions (RDFs) and solvent accessible surface area show increased methane aggregation with the addition of ChCl compared to pure water. Detailed cluster analysis highlights the formation of larger and more compact methane clusters at higher ChCl concentrations. The addition of ChCl induces dewetting of the methane surface, enhancing methane association, as confirmed by preferential interaction parameter calculations for water. Simultaneously, choline molecules cluster around methane, creating a hydrophobic environment that further promotes association. Our microscopic structural investigation shows that the addition of ChCl disrupts the water hydrogen-bond network around methane. Hydrogen bond analysis reveals an increase in choline-choline and a decrease in both water-water and choline-water hydrogen bonds near methane. PMF and association constants obtained from umbrella sampling further confirm the enhanced hydrophobic association between methane in the presence of ChCl compared to pure water. In summary, our findings highlight the crucial role of osmolytes in stabilizing hydrophobic interactions among nonpolar solutes, which has broad implications for various biological processes.