Comparison of the United- and All-Atom Representations of (Halo)alkanes Based on Two Condensed-Phase Force Fields...

The level of accuracy that can be achieved by a force field is influenced by choices made in the interaction-function representation and in the relevant simulation parameters. These choices, referred to here as functional-form variants (FFVs), include for example the model resolution, the charge-derivation procedure, the van der Waals combination rules, the cutoff distance, and the treatment of the long-range interactions. Ideally, assessing the effect of a given FFV on the intrinsic accuracy of the force-field representation requires that only the specific FFV is changed and that this change is performed at an optimal level of parametrization, a requirement that may prove extremely challenging to achieve in practice. Here, we present a first attempt at such a comparison for one specific FFV, namely the choice of a united-atom (UA) versus an all-atom (AA) resolution in a force field for saturated acyclic (halo)alkanes. Two force-field versions (UA vs AA) are optimized in an automated way using the CombiFF approach against 961 experimental values for the pure-liquid densities ρ_liq and vaporization enthalpies ΔH_vap of 591 compounds. For the AA force field, the torsional and third-neighbor Lennard-Jones parameters are also refined based on quantum-mechanical rotational-energy profiles. The comparison between the UA and AA resolutions is also extended to properties that have not been included as parameterization targets, namely the surface-tension coefficient γ, the isothermal compressibility κ, the isobaric thermal-expansion coefficient α, the isobaric heat capacity c, the static relative dielectric permittivity ϵ, the self-diffusion coefficient D, the shear viscosity η, the hydration free energy ΔG_wat, and the free energy of solvation ΔG_che in cyclohexane. For the target properties ρ_liq and ΔH_vap, the UA and AA resolutions reach very similar levels of accuracy after optimization. For the nine other properties, the AA representation leads to more accurate results in terms of η; comparably accurate results in terms of γ, κ, α, ϵ, D, and ΔG_che; and less accurate results in terms of c and ΔG_wat. This work also represents a first step toward the calibration of a GROMOS-compatible force field at the AA resolution.