In the MED model applied here, the binding energy of the selected ligand moiety (or compound) is approximated as the sum of the interaction energies of each pocket residue with the moiety. The MED model has been proven to correlate well with inhibitory activities in a number of protein-ligand complexes (as summarized in ref. 33), including the binding of a TbPTR1 ligand series with varying substituents bound in subpocket D .