Systematic Optimization of a Fragment-Based Force Field against Experimental Pure-Liquid Properties Considering Large Compound Families: Application to Saturated Haloalkanes
Marina P. Oliveira, Maurice M. Andrey, Salomé R. Rieder, Leyla Kern, David F. Hahn, Sereina Riniker, Bruno A. C. Horta, Philippe H. Hünenberger
Abstract
for the calibration (validation) set. The values are lower for the validation set which contains larger molecules (stronger influence of purely aliphatic interactions). The trends in the optimized parameters along the halogen series and across the compound family are in line with chemical intuition based on considerations related to size, polarizability, softness, electronegativity, induction, and hyperconjugation. This observation is particularly remarkable considering that the force-field calibration did not involve any QM calculation. Once the time-consuming task of target-data selection/curation has been performed, the optimization of a force field only takes a few days. As a result, CombiFF enables an easy assessment of the consequences of functional-form decisions on the accuracy of a force field at an optimal level of parametrization.