The "mixture only" optimization task optimizes the LJ parameters against a set of 195 physical properties (𝜌 𝐿 (𝑥), Δ𝐻 𝑚𝑖𝑥 (𝑥)) for the set of molecular pairs shown in Figure . These molecule pairs are drawn from the same set of molecules as used in the "pure only" training set. All measurements here are selected from the NIST ThermoML archive, and are selected at temperatures and pressures close to ambient (∼ 1 atm, 273.15-318.15 K). We select measurements at concentrations with 0.05 mole fraction of 3 target concentrations for each mixture, where available: (𝑥 1 = 0.25, 𝑥 2 = 0.75), (𝑥 1 = 0.5, 𝑥 2 = 0.5), (𝑥 1 = 0.75, 𝑥 2 = 0.25). If no measurements are available within 0.05 mole fraction of any target concentration, no data point is selected for that target concentration. A list of the mixtures in the "mixture only" training set is available in the Supporting Information, Section S1. For this optimization task, we performed an initial optimization using 𝑁 = 20 initial points, due to the increased complexity of the training set. After this optimization, we performed a second optimization using 𝑁 = 10 initial points, in order to test whether a more data-sparse optimization could be successful. For the 𝑁 = 10 replicate, 9 initial points are subsampled from the 19 LHS points used in the 𝑁 = 20 replicate to minimize simulation expense.