Binding of arachidonic acid and two flavonoid inhibitors to human 12- and 15-lipoxygenases: a steered molecular dynamics study.

The lipoxygenases (LOX) are a family of non-heme iron-containing dioxygenases which catalyze the stereospecific insertion of molecular oxygen into arachidonic acid, leading to hydroxy derivatives as end products. In this work, we docked arachidonic acid and two of its competitive inhibitors, flavonoids baicalein and quercetin, into the binding pockets of human 12- and 15-lipoxygenase. Steered molecular dynamics (SMD) simulations were employed to study the unbinding processes of the substrate and inhibitors from the two isoforms.