For construction of the PLIP score, interactions formed in the available protein-fragment complex crystal structures were one-hot encoded to form a reference vector of desired interactions (here, hydrophobic, hydrogen-bonding, π-stacking, and salt bridge were all identified). A similar vector was constructed for the designed de novo compound, and its Tanimoto similarity to the reference vector used as the objective for optimisation. It has been argued that combining information from various properties can also be advantageous, for example by using pharmacophore constraints in combination with docking scores, and we make use here of a simple, combined score (CS):