Assessing the thermodynamic signatures of hydrophobic hydration for several common water models

Abstract

Following the conclusions of an information theory analysis that hydrophobic hydration is dictated by the equation of state of liquid water, we perform simulations of ten different water models to examine the correlation between the fidelity of each model to the experimental density of liquid water and the accuracy of its description of methane hydration. We find that the three- and five-point water models provide an inferior description of both the liquid density and methane solubility compared to the four-point water models. Of the four-point water models, TIP4P/2005 provides the best description of both the aqueous equation-of-state and methane hydration thermodynamics. When the optimized potentials for liquid simulation united-atom description for methane is used, we find that while the entropy and heat capacity of methane hydration are in excellent agreement with experiment, the chemical potential and enthalpy are systematically shifted upwards. We subsequently reoptimize the methane interaction to accurately reproduce the experimental solubilities as a function of temperature by accounting for missing attractive interactions.

A fully atomistic computer simulation study of cold denaturation of a β-hairpin

“…One possible source of such biases is the overestimation of hydrophobic interactions by the current force field. This view is in line with prior simulation results that showed that the hydration free energies of non-polar molecules are systematically overestimated 19,[21][22][23] . In an effort to remedy such discrepancies, relevant protein/water interaction terms in the force field may need to be further optimized.…”

“…As for the force field, we use the ff99sb-nmr1-ildn force field (nmr1) 13,14 for the protein segment. The nmr1 force field is a highly optimized version of its parent force field ff99sb 13 18,19 . In contrast with the tip3p model, the tip4p/2005 model 16 (an improved version of its parent tip4p model 15 ) can reproduce various experimental temperature-dependent properties.…”

Entropy and enthalpy convergence of hydrophobic solvation beyond the hard-sphere limit

“…This stands in contrast to the common view according to which the solvation of hydrophilic solutes is purely enthalpic and characterized by vanishing heat capacity. 22,23 We note, that the solvation free energies for a Lennard-Jones parameterization of methane 40 are well within the spread observed in Fig. 10(e).…”

“…(17) is not very serious, as shown in Figs. 8(c) and 8(d), one concludes that it is mostly the variation in ρ that causes the differences in the solvation free energy, 27,37,40 as seen in Figs. 8(a) and 8(b).…”

“…Theoretically, the temperature dependence of hydrophobic hydration has been studied by various methods, [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] mostly focusing on the solvation of simple model solutes such as hard spheres 27, 28, 30-33, 35, 39 or Lennard-Jones particles. 26,29,34,37,40 Using a Gaussian model for particle number fluctuations in atomic-scale cavities in conjunction with simulated water radial distribution functions, convergence temperatures of about T * S ≈ 400 K for small hardsphere solutes of different radii, close to the experimental results, were obtained. 27,28,31 The model allowed a simple interpretation of this phenomenon in terms of particle number fluctuations, water density variation, and to a limited extent the isothermal compressibility of water.…”