Docking scores of (S)-naproxen and benzbromarone effectors and resulting changes caused by simultaneous binding
Ligand(s) | GlideScorea | Distance of Naproxen Methoxy Protons from Heme Ironb | ||
|---|---|---|---|---|
| R108 Sitec | F476 Sitec | |||
| Å | ||||
| Naproxen | -8.35 | 5.71 | ||
| Two naproxens | -8.97 | -5.32 | 4.78 | |
| Benz(meth)arone | -7.31 | |||
| Benzbromarone | -8.19 | |||
| Benz(meth)arone plus naproxen | -7.31 (naproxen) | -7.62 (benz(meth)arone) | 5.10 | |
| -6.50 (benz(meth)arone) | -7.41 (naproxen) | |||
| Benzbromarone plus naproxen | -9.10 (naproxen) | -6.97 (benzbromarone) | 4.77 | |
|
| -6.58 (benzbromarone) | -6.97 (naproxen) |
| |
↵ a Top docking scores obtained from Glide as described under Materials and Methods; more negative values reflect higher binding affinity.
↵ b Average taken from top scoring conformation of naproxen at the R108 site; naproxen was not favored to bind with its metabolized position near the heme in the F476 site.
↵ c Location of the two binding regions identified by docking. The R108 site places the substrate naproxen nearest the heme for oxidation. When a second naproxen molecule or an effector is included, the corresponding effects on the affinity of each ligand can be calculated.