Analysis of neo-pentane–urea pair potentials of mean force in aqueous urea

Abstract

Urea is often used as a denaturant in protein (un)folding studies because it alters the way hydrophobic solutes and water affect one another. The solvation structure of neo-pentane and urea in 6.9 M urea aqueous solution are investigated by analysing the neo-pentane–urea potential of mean force (PMF) as a function of the neo-pentane–urea separation obtained from molecular dynamics simulations. The PMF is decomposed into its enthalpic (H) and entropic (S) contributions, which are further separated into solute (neo-pentane–urea pair) and solvent (urea, water) contributions. Statistical-mechanical, enthalpic and entropic contributions arising from solvent–solvent interactions do not contribute directly to the PMF because they exactly cancel each other. By excluding the solvent–solvent parts, it is seen that the first minimum in the PMF is due to a combination of contributions coming from the neo-pentane–urea pair self-enthalpy and from the entropy related to the interaction of the neo-pentane–urea pair solute with the remaining solvent molecules. The enthalpy of a neo-pentane–urea pair solute and the remaining urea and water molecules acts against neo-pentane–urea association because this association prohibits the remaining solvent from interacting with the urea molecule belonging to the solute. In addition, ranges of interest in the PMF are structurally and energetically characterized in terms of hydrogen bonding, non-bonded energies and number of neighbouring molecules of a given type. This leads to a consistent thermodynamic and structural picture of hydrophobic co-solvent interaction in aqueous urea.