Force fields optimized against experimental data for large compound families using CombiFF: Validation considering non-target properties and polyfunctional compounds

Abstract

The CombiFF scheme is a workflow for the automated calibration of force-field parameters against condensed-phase experimental data considering simultaneously entire classes of organic molecules. The main steps of this scheme are: (i) selection of a molecule family; (ii) enumeration of all isomers; (iii) query for experimental data; (iv) automatic construction of the molecular topologies; (v) iterative refinement of the force-field parameters considering the entire family. In two recent articles, CombiFF was applied to the design of GROMOS-compatible united-atom force fields for the saturated acyclic haloalkanes and for saturated acyclic compounds involving eight common chemical functional groups of oxygen and nitrogen. This calibration and the subsequent initial validation involved two limitations: (i) the experimental data considered was restricted to values for the pure-liquid density ρliq and the vaporization enthalpy ΔHvap of the compounds; (ii) beyond monofunctional compounds, the training set only involved homo-polyhaloalkanes (possibly mixing halogen types) in the first study, and homo-polyfunctional compounds of the considered oxygen or nitrogen functional groups (no mixing of different group types) in the second one. The goal of this article is to further test the accuracy of CombiFF-generated force fields by extending the validation to: (i) nine additional properties that were not used as optimization targets (pure-liquid thermodynamic, dielectric and transport properties, as well as solvation properties); (ii) hetero-polyfunctional molecules that were not included in the calibration and initial validation sets. The results for the nine additional properties show good agreement with experiment, except for the shear viscosity and the dielectric permittivity. There, larger discrepancies are observed, likely due to the united-atom representation adopted for the aliphatic groups and to the implicit treatment of electronic polarization effects. The results for the hetero-polyfunctional molecules also show reasonable agreement with experiment in terms of the monitored properties.