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.

GROMOS++ is a set of C++ programs for pre- and postprocessing of molecular dynamics simulation trajectories and as such is part of the GROningen MOlecular Simulation software for (bio)molecular simulation. It contains more than 70 programs that can be used to prepare data for the production of molecular simulation trajectories and to analyze these. These programs are reviewed and the various structural, dynamic, and thermodynamic quantities that can be analyzed using time series, correlation functions, and distributions are described together with technical aspects of their implementation in GROMOS. A few examples of the use of GROMOS++ for the analysis of MD trajectories are given. A full list of all GROMOS++ programs, together with an indication of their capabilities, is given in the Appendix .

A new parameter set (53A6OXY) is developed for the GROMOS force field, that combines reoptimized parameters for the oxygen-containing chemical functions (alcohols, ethers, aldehydes, ketones, carboxylic acids, and esters) with the current biomolecular force field version (53A6) for all other functions. In the context of oxygen-containing functions, the 53A6OXY parameter set is obtained by optimization of simulated pure-liquid properties, namely the density ρliq and enthalpy of vaporization ΔHvap, as well as solvation properties, namely the free energies of solvation in water ΔGwat and in cyclohexane ΔGche, against experimental data for 10 selected organic compounds, and further tested for 25 other compounds. The simultaneous refinement of atomic charges and Lennard-Jones interaction parameters against the four mentioned types of properties provides a single parameter set for the simulation of both liquid and biomolecular systems. Small changes in the covalent parameters controlling the geometry of the oxygen-containing chemical functions are also undertaken. The new 53A6OXY force-field parameters reproduce the mentioned experimental data within root-mean-square deviations of 22.4 kg m(-3) (ρliq), 3.1 kJ mol(-1) (ΔHvap), 3.0 kJ mol(-1) (ΔGwat), and 1.7 kJ mol(-1) (ΔGche) for the 35 compounds considered.