Design 9 (∆G = -17 ± 2 kcal/mol) features halogens on both sides, unlike its closest neighbor, molecule 13 (∆G = -10.5 ± 0.7 kcal/mol), from which it also differs in the moiety attached to the pyridonic ring (Figure ). When inspecting the predicted binding pose, it can be observed that the aromatic ring with halogen substituents, hydroxyl, and carbonyl of pyridone are situated in the same region of the binding groove (Figure ). The difference in ∆G values (approximately 6.5 kcal/mol, in favor of design 9) could be ascribed, like with molecule 3, to the presence of halogens in the lower binding pocket region. This might also explain the high predicted affinity of design 10 (∆G = -15 ± 2 kcal/mol) -which differs from 9 by a carbonyl and a methyl group.