After only 5 iterations, the overall R 2 has increased from 0.53 to 0.87 and the root of mean squared error (RMSE) dropped from 1.26 kcal/mol to 0.73 kcal/mol (as shown in Figure and Table ). This performance boost can be attributed to the significant improvement of outliers, such as 5a→5c. This result clearly demonstrates the advantage brought by DMFF, essentially allowing us to further improve the state-of-the-art model without any chemical intuition.