Figure ) shows the highest scoring compound from this run, with a predicted affinity of 88 nM. The compound extends hydrophobic contacts into the S3 and S1' pockets, for ex- ample with Met165 and Thr25, but despite this does not form any specific polar interactions (other than the original core interaction with His163). Since an early fragment screen had provided valuable information about the nature of potential protein-ligand interactions in this binding pocket, we sought to reduce the reliance on the gnina scoring function and drive the active learning towards compounds that recovered known crystallographic information (see Methods). Figure ) shows the top-scoring compound, as defined by the Tanimoto similarity to the vector of reference interactions. In this case, the grown molecule forms additional hydrogen bonding interactions with Asn142, Gly143, Ser144, Cys145 and Glu166, and hydrophobic interactions with Thr25 and Glu166. The majority of these interactions are recapitulated by, for example, fragments PDB: 5RGI and 5RF7 (Figure )).