All simulations used to estimate physical properties in the LJ training and test datasets are performed with the OpenFF Evaluator 70 software package version 0.3.4, 76 using the default simulation workflow schemas, described below. Where possible, simulation results are used to estimate multiple properties (e.g. using the same pure liquid simulations in both a 𝜌 and Δ𝐻 𝑚𝑖𝑥 calculation). All liquid simulations used in the optimization are performed with 1000 molecule simulation boxes created with PackMOL. After energy minimization and a 0.2 ns equilibration run, each box is simulated for 2 ns in the NPT ensemble. Ensemble averages used in physical property calculations are taken from uncorrelated snapshots, subsampled with the method proposed by Chodera. Physical property calculations are calculated with the same procedures used in Boothroyd et al.