Figure shows performance on the training set before and after LJ refitting, focusing on several notable cases where the optimization was successful or unsuccessful; a similar plot for all training data is available in SI Figure . Figure shows the force field with refitted LJ parameters but unchanged valence parameters, referred to as vdw-v1. The performance of vdw-v1 on liquid state properties would be similar to Sage 2.0.0, as these properties are most dependent on LJ parameters and electrostatics, which are unchanged between vdw-v1 and Sage 2.0.0. Additionally, the performance of vdw-v1 on the solvation/transfer free energy benchmark set described in Section 3.2 (shown in Supporting Information Table ) was not statistically different than that of Sage 2.0.0. The data in this table is presented not as the final force field, as the valence parameters in vdw- were not yet reoptimized in the presence of new van der Waals parameters, but to illustrate the direct effect of LJ refitting on performance with mixture data. The other substantial change is the epsilon for the hydroxyl hydrogen [#1:1]-[#8] type, which is less notable on an absolute scale, as it is reduced from 5.27×10 -5 kcal/mol to 1.22×10 -5 kcal/mol. This parameter was discussed previously in Mobley et al., and its value is essentially designed to be "small but non-zero", in order to avoid unphysical effects; it did not originally result from a fit to condensed phase properties. We therefore do not assign a significant physical meaning to the reduction of this value.