As this study was aimed at investigating the binding of fatty acid and peptide substrates of the enzyme, independent hLTA4H-LTA4 (L-LTA4) and hLTA4H-RAR (L-RAR) complexes were prepared. The LTA4 of AA cascade is the natural substrate of the enzyme but no 3D structural information was available for its binding from X-ray studies. Some previous studies have reported the proposed binding of this fatty acid substrate at the active site of the enzyme. In this study, molecular docking methodology using GOLD 5.0.1 program was employed to obtain the reliable binding mode of LTA4. The GOLD program from Cambridge Crystallographic Data Centre, UK uses a genetic algorithm to dock the small molecules into the protein active site [46, 55] . The GOLD allows for a full range of flexibility of the ligands and partial flexibility of the protein. One of the crystal structures of hLTA4H bound with most active inhibitor (PDB ID: 3FUN) solved at high resolution was used in molecular docking. The bound inhibitor of this crystal structure was removed and the apoform of this enzyme was subjected to MD simulations with the parameters discussed below. The representative structure with a RMSD value close to the average structure of last 3 ns of the 5 ns MD simulations was selected and utilized in molecular docking experiments. The active site was defined with a 10 Å radius around the bound inhibitor. The ten top-scoring conformations of every ligand were saved at the end of the calculation. Early termination option was used to skip the genetic optimization calculation when any five conformations of a particular compound were predicted within an RMS deviation value of 1.5 Å . The GOLD fitness score is calculated from the contributions of hydrogen bond and van der Waals interactions between the protein and ligand, intramolecular hydrogen bonds and strains of the ligand [56] . Protein-ligand interactions were analyzed using DS and Molegro Molecule Viewer [57] . The best pose was selected based on the molecular interactions and the distance between epoxy group of LTA4 and metal ion (Zn 2+ ) present in the active site as well as the location of its carboxylate group which interacts with the carboxylate recognition residues R563 and K565. Finally, the enzyme-LTA4 complex was prepared to be used in further steps in this study.