The CYP 3A4 cavity is a large featureless hole with a planar heme iron network on one side. The thought to lessen the interaction with the enzyme is to push the bound ligand farther away from the heme iron which is a point of higher interaction. This can be done somewhat at the cost of reducing the extent of the conjugation, and the arene rings are desired for their electronic properties in holding a deposited charge. Detailed examination of the ligand and atomic distributions of scores to CYP 3A4 point to a good area of modification. The scores of 20000 docking runs are given in Figure (a) together with a multi a*exp(-|x-b|/c) curve fit highlighting the 4 primary binding modes. Note that the multi-peak distribution, which can be modeled by a 4-exp||, Figure (a). A slightly better fit which includes the bump at high score is modeled by a 5-exp|| curve in Figure (b). The fit parameters of the latter are given in Figure (c). The highest interacting binding modes at 82.9 and 85.8 start approximately at 78.3 where the 3 others are approximately centered at 70.8 and 73.5, 75.1. For a curve fitting comparison, a 4 Gaussian fit is presented in Figure ; this fit shows the differences in using a multi-a*exp(-|x-b|/c) versus a multi-normal distribution. The oxygen atom O1 is central to the metabolic binding of BAM-15 to the liver enzyme CYP 3A4 and is a significant point of symmetry in the small molecule. The atomic score distributions of the 3 atoms in the N-O-N region contributing to the 1 st binding mode, i.e., in Figure ) those with total scores >78.3, are shown in Figure . The oxygen O1 has a very high average score of >4 due to the iron network, but its 2 connected neighbors N2 and N25 are exceptionally high in score with 1 of the 2 strongly bound to the heme iron. This high interaction is due to the proximity to the heme iron network, the presence of hydrogen bonds, and the modeled interaction between the Fe atom and a nitrogen. The distributions of N2 and N25 are the same, reflective of BAM-15's symmetry.