Docking and Molecular Dynamics Simulations Reveal A Possible Site of Interaction of Olive Leaf Extract Hydroxytyrosol with Polyunsaturated Fatty Acid 5-Lipoxygenase Human Enzyme

Abstract

The polyphenol hydroxytyrosol (HT), a molecule easily extracted from olive oil production waste, has well known antioxidant and anti-inflammatory properties. In literature various bioassays points to a clear inhibitory effects on the polyunsaturated fatty acid 5-lipoxygenase enzyme (LOX5) which is a current target for pharmaceutical intervention for various inflammatory diseases. We have investigated the hypothesis of direct interaction of HT with LOX5 through blind docking and a 200 nanoseconds long molecular dynamics. Analysis of the results highlights the stability of the interaction of HT in the putative binding site with LOX5. This is in accord with the hypothesis of an allosteric way of action of HT to inhibit the activity of the LOX5 also suggesting the use of HT structure as a scaffold to design LOX5 inhibitors with improved activity and specificity.