Most of the 2-run grandchildren predicted a unique 4 ring scaffold docking to the same AB cavity (Figure , green sticks), despite many other cavity possibilities offered by the ADV blind-docking wide grid. The 2-run top-grandchild was 4670 predicting ~ 16.7 nM affinity (Table ). One of its extreme rings predicted 2 Cl atoms and a characteristic short -CO-N-SO2 -link in between 2 other extreme rings, an heritage of the 16153 parent (Figure , 4670 right). Seven oxygens contributed to lowering its LogP to 2.0 (Table ). The main interactions between 4670 and the AB interface cavity, targeted 115 R at both A and B chains by two Hydrogen bonds (Figure , 4670 left), and salt bridges between the A and B chains ( 119 D-115 R and 115 R-92 E, respectively). There were also other amino acids implicated in the AB interface that were targeted by 4670 such as those forming Hydrogen bonds to 94 K and 93 P as well as 120 F (Hydrogen bond 120 F-53 K). The predicted 4670 competition formed by two Hydrogen bond predictions with 115 R, together with the rest of interactions may explain its nanoMolar affinities.