Interaction simulation of Lipoxygenase with arachidonate acid using NAMD

Lipoxygenase (LOX) family is believed as the major cause of pathological symptoms in asthma by biosynthesis of leukotrienes. The physiological function is known as firstly producing 8R-HPETE (derived from arachidonate acid, referred as AA), which is transformed in further enzymatic step into leukotrienes. However, much less detail is known about the role of 5-Lox in the inflammatory reaction. We have used the 1.85Å resolution structure of a wild coral Lipoxygenase (8R-LOX) (with 41% sequence identical to the human arachidonate 5-LOX) as a foundation to model the interactions between 8R-Lox and its substrate AA, and its binding site was identified using ICM. In this research, the 8R-Lox:AA complex obtained was refined and analyzed by molecular dynamic method (NAMD). Parameterization scheme for unknown structure of non-heme iron ligated by a series of residues was developed using VMD paratool plugin. All quantum mechanical calculation were performed by Gaussian03 with the Becke3LYP functional at 6-31G(d) basis set.