In the second case (Fig. , orange), we apply a Gaussian noise of standard deviation 20 kcal/mol for molecules with positive enthalpy and Gaussian noise of standard deviation 2 kcal/mol for molecules with negative enthalpy. For this case we contrast the performance of uncertainty estimation by ensembling (bottom left) with the meanvariance estimation method (bottom right). As we discuss in a later section, ensembling is a measurement of variance error and does not directly incorporate noise error. Ensembling also requires a scaling calibration to match the magnitude of errors unless variance error dominates, so the ensemble uncertainty was scaled so that the ensemble and mean-variance estimation would have the same average value. In this case, the ensembling method of uncertainty estimation does a poor job of distinguishing the noise regimes, with a mean uncertainty 10.6 kcal/mol for molecules with negative original target enthalpy and mean uncertainty 11.5 kcal/mol for molecules with positive original target enthalpy. The mean-variance estimation is able to distinguish and quantify the noise regimes appropriately, with mean uncertainty 2.4 kcal/mol for molecules with negative original target enthalpy and mean uncertainty 19.5 kcal/mol for molecules with positive original target enthalpy. This example shows how mean-variance estimation can distinguish between noise regimes better than a method suited to other error types.