As described in Section 3, three surrogate model architectures in combination with two different fingerprint representations were explored. We evaluated the performance of each surrogate model/fingerprint combination using 6-fold nested cross-validation on the 140 cycloaddition reactions of the original BH9 dataset. Morgan fingerprints clearly outperform DRFP, a lower radius (r =1 and r =2) results in lower errors than higher ones (r =3), and increasing the number of bits, decreases the error in our calculations.