Association of Small Hydrophobic Solute in Presence of the Osmolytes Urea and Trimethylamine-N-oxide

Abstract

Influences of two naturally occurring osmolytes, urea and trimethylamine-N-oxide (TMAO), on hydrophobic interactions of methane are investigated by performing molecular dynamics (MD) simulations. In this study, we have used two different models of methane: one is of single united site (UA), and the other contains 5-sites (AA). We observe that two methane models behave similarly in pure water and in aqueous osmolyte solutions except for the fact that AA model of methane behaves slight differently in aqueous binary urea solution. Our potentials of mean force (PMF) calculations followed by association constant estimation and cluster structure analyses suggest urea-induced enhancement of methane association for the methane AA model. For both models, we observe the dehydration of methane molecules in presence of osmolytes. We also find the collapse of the second shell of water by urea and water structure enhancement by TMAO molecules. Our preferential interaction parameter calculations show that in binary aqueous urea solution methane molecules are expelled by urea molecules and this effect is more pronounced for the AA model. On the other hand, in binary aqueous TMAO solution, methane prefers to interact more with TMAO than water. Our water orientational structure calculations show that the orientation of water molecules near to hydrophobic moiety is anisotropic and osmolytes have a negligible effect on it. We also observe the osmolyte-induced water-water hydrogen bond lifetime increase in the hydration shell of methane as well as in the subsequent layers.