Systematic Optimization of a Fragment-Based Force Field against Experimental Pure-Liquid Properties Considering Large Compound Families: Application to Saturated Haloalkanes.

Direct optimization against experimental condensed-phase properties concerning small organic molecules still represents the most reliable way to calibrate the empirical parameters of a force field. However, compared to a corresponding calibration against quantum-mechanical (QM) calculations concerning isolated molecules, this approach is typically very tedious and time-consuming. The present article describes an integrated scheme for the automated refinement of force-field parameters against experimental condensed-phase data, considering entire classes of organic molecules constructed using a fragment library combinatorial isomer enumeration.