Compared to the RDKit physicochemical descriptors, models trained with VSURF descriptors consistently performed worse on external sets (Table ). The difference in performance between the random and realistic split is noticeable when observing the physiochemical descriptors (RF: 0.77 vs. 0.53). More importantly, this drop in performance is also seen in the R2 values of the corresponding external test sets (RF: 0.78 vs. 0.51). When looking at the VSURF descriptors, the decrease in performance is only observed in the external test sets, not in cross-validation. This might be due to overfitting of the models trained with the VSURF descriptors and the better generalizability of the physiochemical descriptors.