For optimization runs without these outlier changes to parameters, such as run 1, the results are improved, with a decrease in test set Δ𝐻 𝑣𝑎𝑝 from an initial value in OpenFF 1.0.0 of 7.52 kJ/mol (95% CI 6.42, 8.53) to a value after fitting of 3.41 kJ/mol (95% CI 1.94, 4.68), outperforming the simulation-only optimization value of 5.25 kJ/mol (95% CI 4. . This improvement in Δ𝐻 𝑣𝑎𝑝 , following the improvement in the training set, suggests that the more aggressive multi-fidelity optimization was able to adjust parameters in a way that results in better prediction of Δ𝐻 𝑣𝑎𝑝 . For the other properties in the test set, run 1 improves over OpenFF 1.0.0 in each case, and is slightly improved over the simulation-only optimization for 𝜌 𝐿 and 𝜌 𝐿 (𝑥). The optimization does perform slightly worse than the simulation-only optimization for Δ𝐻 𝑚𝑖𝑥 , which likely reflects the lack of regularization and stronger focus on Δ𝐻 𝑣𝑎𝑝 .