In the case of plasmepsin 2, the best rank obtained was just 420 (TanimotoCombo score). This target is characterized by a highly flexible ligand binding site to which small molecules are known to bind in several distinct modes. The fact that there were only 15 non-CSMs recorded for that target may contribute to the difficulties in recognizing CSMs active on this protein (note however that coagulation factor XI was correctly identified as the target of two out of the ten CSMs and ranked among the top-3 positions even though the target is represented by only 15 non-CSMs in the knowledge base).