Binding investigation of human 5-lipoxygenase with its inhibitors by SPR technology correlating with molecular docking simulation

The binding features of a series of 5-lipoxygenase (5-LOX) inhibitors (caffeic acid, NDGA, AA-861, CDC, esculetin, gossypol and phenidone) to human 5-LOX have been studied by using surface plasmon resonance biosensor (SPR) technology based Biacore 3000 and molecular docking simulation analyses. The SPR results showed that the equilibrium dissociation constant (K-D) values evaluated by Biacore 3000 for the inhibitors showed a good correlation with its reported IC50, suggesting that SPR technology might be applicable as a direct assay method in screening new 5-LOX inhibitors at an early stage. In addition, the 3D structural model of 5-LOX was generated according to the crystal structure of rabbit reticulocyte 15-lipoxygenase, and the molecular docking simulation analyses revealed that the predicted binding free energies for the inhibitors correlated well with the K-D values measured by SPR assay, which implies the correctness of the constructed 3D structural model of 5-LOX. This current work has potential for application in structure-based 5-LOX inhibitor discovery.