A GROMOS-Compatible Force Field for Small Organic Molecules in the Condensed Phase: The 2016H66 Parameter Set.

ABSTRACT

This article reports on the calibration and validation of a new GROMOS-compatible parameter set 2016H66 for small organic molecules in the condensed phase. The calibration is based on 62 organic molecules spanning the chemical functions alcohol, ether, aldehyde, ketone, carboxylic acid, ester, amine, amide, thiol, sulfide, and disulfide, as well as aromatic compounds and nucleic-acid bases. For 57 organic compounds, the calibration targets are the experimental pure-liquid density ρliq and the vaporization enthalpy ΔHvap, as well as the hydration free energy ΔGwat and the solvation free energy ΔGche in cyclohexane, at atmospheric pressure and at (or close to) room temperature. The final root-mean-square deviations (RMSD) for these four quantities over the set of compounds are 32.4 kg m(-3), 3.5 kJ mol(-1), 4.1 kJ mol(-1), and 2.1 kJ mol(-1), respectively, and the corresponding average deviations (AVED) are 1.0 kg m(-3), 0.2 kJ mol(-1), 2.6 kJ mol(-1), and 1.0 kJ mol(-1), respectively. For the five nucleic-acid bases, the parametrization is performed by transferring the final 2016H66 parameters from analogous organic compounds followed by a slight readjustment of the charges to reproduce the experimental water-to-chloroform transfer free energies ΔGtrn. The final RMSD for this quantity over the five bases is 1.7 kJ mol(-1), and the corresponding AVED is 0.8 kJ mol(-1). As an initial validation of the 2016H66 set, seven additional thermodynamic, transport, and dielectric properties are calculated for the 57 organic compounds in the liquid phase. The agreement with experiment in terms of these additional properties is found to be reasonable, with significant deviations typically affecting either a specific chemical function or a specific molecule. This suggests that in most cases, a classical force-field description along with a careful parametrization against ρliq, ΔHvap, ΔGwat, and ΔGche results in a model that appropriately describes the liquid in terms of a wide spectrum of its physical properties.