We reduced the computational cost further by reducing the number of energy evaluations required to estimate E min . If our hypothesis about synthesized molecules being lower in energy is true, then the the set of already-reported molecules should contain the lowest-energy isomer or at least one within a small energy difference of the true minimum isomer. We should therefore be able to estimate E min by only comparing against the molecules found in PubChem. The change in classification accuracy for comparing to PubChem instead of all molecules is negligible for our QM9 test set and requires an average 40 energies per E min computation instead of 180. In practice, one could even compare against both PubChem molecules and a reduced sample of generated structures to achieve a tradeoff between accuracy and cost to compute E min . Comparing against only PubChem also bypasses the need to generate example molecules, which can require days for molecules with over 20 non-hydrogen atoms.