In addition, we investigated property space occupied by AHC generated de novo molecules (Figure ) which shows that the property space is still maintained in all cases except for increasing molecular weight seen with OX1R. Here, the mean is slightly above 350 Da which is however consistent with OX1R antagonists . In fact, in some cases (for OPRM1 in the case of molecular weight and number of rotatable bonds, and for OX1R in the case of the number of rotatable bonds) the property space shifts in the opposite direction to that which would be expected by an exploitation of the scoring function. Overall, de novo chemistry is still reasonable and sufficiently regularized by AHC in combination with DF2 and can even be more heavily regularized by reducing σ to 30, yet still outperform REINVENT at all σ values as seen in Experiment 1.