Computer Simulation of Urea−Water Mixtures:  A Test of Force Field Parameters for Use in Biomolecular Simulation

Abstract

A molecular model for urea to be used in conjunction with the simple point charge (SPC) model for liquid water in protein denaturation studies is validated by comparison of molecular dynamics (MD) simulation results to experimental data at 298 K as a function of urea mole fraction. The density, enthalpy of mixing, free enthalpy of urea hydration, and urea diffusion show very good agreement with the experimental values. The experimental error in the free enthalpy of hydration, which is dominated by the inaccuracy of the vapor pressure of solid urea, is larger than the simulation error. This limited accuracy does not allow a check of the nonideality of the solution. Free enthalpies have been obtained by thermodynamic integration. The importance of a correct use of the combinatorial factor in the partition function when interpreting simulation results obtained by thermodynamic integration is discussed. The tested, GROMOS96 compatible, force field parameters form a good basis for biomolecular simulations using urea-water mixtures.

Preferential Solvation in Urea Solutions at Different Concentrations: Properties from Simulation Studies

“…29,30 Our diffusion constants of OPLS urea in TIP3P are in good accord with those measured in SPC water. 28 The SPC/E water model is a revised version of the SPC model and shows good agreement for the diffusion constant of urea with experimental values although the water still moves a bit too fast. 13,27 Due to a greater slope, as the urea concentration increases, diffusion constants of both urea and water are in somewhat better agreement with experimental values at high concentrations.…”

Biomolecular Modeling: Goals, Problems, Perspectives

“…The thermodynamic properties, such as energy and density of mixing, are of particular importance when the free energy of solvation and folding of solutes is to be calculated. [8,9,[41][42][43] The properties of a mixture of two solvents need not be a linear function of its composition, as illustrated for water/ dimethyl sulfoxide (DMSO) mixtures in Figure 9. Only the dielectric permittivity e shows a linear behavior, while the other properties considered show different types of nonlinearity.…”

Chemical potential of liquids and mixtures via adaptive resolution simulation

“…Since it would be too expensive to do the convergence tests for all concentrations, we simply use a large cut-off 1.4 nm for the concentration dependency study of TBA/water. Electrostatic interactions were calculated using the reaction-field term [27] with a dielectric permittivity of 54 for urea in SPC water [17], 64.8 for TBA in SPC water [18], 61 for other solutes in SPC water, 19 for methanol and 46 for DMSO as the solvent [15].…”