Force Field Benchmark of Organic Liquids: Density, Enthalpy of Vaporization, Heat Capacities, Surface Tension, Isothermal Compressibility, Volumetric Expansion Coefficient, and Dielectric Constant

Abstract

The chemical composition of small organic molecules is often very similar to amino acid side chains or the bases in nucleic acids, and hence there is no a priori reason why a molecular mechanics force field could not describe both organic liquids and biomolecules with a single parameter set. Here, we devise a benchmark for force fields in order to test the ability of existing force fields to reproduce some key properties of organic liquids, namely, the density, enthalpy of vaporization, the surface tension, the heat capacity at constant volume and pressure, the isothermal compressibility, the volumetric expansion coefficient, and the static dielectric constant. Well over 1200 experimental measurements were used for comparison to the simulations of 146 organic liquids. Novel polynomial interpolations of the dielectric constant (32 molecules), heat capacity at constant pressure (three molecules), and the isothermal compressibility (53 molecules) as a function of the temperature have been made, based on experimental data, in order to be able to compare simulation results to them. To compute the heat capacities, we applied the two phase thermodynamics method (Lin et al. J. Chem. Phys.2003, 119, 11792), which allows one to compute thermodynamic properties on the basis of the density of states as derived from the velocity autocorrelation function. The method is implemented in a new utility within the GROMACS molecular simulation package, named g_dos, and a detailed exposé of the underlying equations is presented. The purpose of this work is to establish the state of the art of two popular force fields, OPLS/AA (all-atom optimized potential for liquid simulation) and GAFF (generalized Amber force field), to find common bottlenecks, i.e., particularly difficult molecules, and to serve as a reference point for future force field development. To make for a fair playing field, all molecules were evaluated with the same parameter settings, such as thermostats and barostats, treatment of electrostatic interactions, and system size (1000 molecules). The densities and enthalpy of vaporization from an independent data set based on simulations using the CHARMM General Force Field (CGenFF) presented by Vanommeslaeghe et al. (J. Comput. Chem.2010, 31, 671) are included for comparison. We find that, overall, the OPLS/AA force field performs somewhat better than GAFF, but there are significant issues with reproduction of the surface tension and dielectric constants for both force fields.

Experimental and Computational Study of BODIPY Dye-Labeled Cavitand Dynamics

“…15 Chloroform parameters (OPLS) and liquid structure coordinates were obtained from virtualchemistry.org. 16 …”

Organic molecules on the surface of water droplets – an energetic perspective

“…Details about how the structures and the topologies were generated, as well as how well the force field performs for such molecules in the liquid phase were presented recently by Caleman et al 54 .…”

“…The root mean square deviation from experiment were lowest for both the combinations of OPLS/AA with SPC and GAFF with TIP3P. Furthermore, properties of the pure liquids were computed (see Supporting Information), following the recipe from our recent benchmark study 54 . Density as well as enthalpy of vaporization were reproduced slightly better for the OPLS/AA liquids and therefore we selected the OPLS/AA force field in combination with the SPC water model for the following calculations.…”

Evaluation of solvation free energies for small molecules with the AMOEBA polarizable force field

“…Recently, Caleman et al evaluated the performance of GAFF32 and OPLS/AA33 in organic solvents 34. They benchmarked the force fields by computing liquid properties such as density, enthalpy of vaporization, heat capacity, surface tension, isothermal compressibility, volumetric expansion coefficient, and dielectric constant of ∼150 organic liquids.…”