At the end of the five iterations several ligands with computed binding free energies below -17 kcal/mol have been found, while the lowest binding free energy of the experimentally known ligands with this scaffold was above -14 kcal/mol (Fig. ). The best binding ligands found in the prospective library are depicted in Fig. . All the high affinity ligands show a similar pattern of substitution at the same functional group. A benzene ring serves as a linker to the scaffold and two groups decorate the ring: a single halogen atom at the 4 or 5 ring position and a longer flexible hydrophobic group that sometimes also contains an electronegative atom.