This study aimed to investigate the 3-D structures and ligands binding features of 5-Lipoxygenase Enzyme (5-LO) with natural substrate, arachidonic acid, and commercial asthma drug, Zileuton. In order to understand about molecular mechanism of 5-LO and be able to use those information in further development of alternative asthma drugs. The 3-D crystal structure of human 5-LO enzyme complex with arachidonic acid is available in protein data bank but there are some part of 5-LO structure that not complete. Therefore, we only extracted arachidonic acid structure out and selected another complete 5-LO crystal structure as host for molecular docking, then used AMBER force field for 5-LO structural optimization. After that, Molecular docking calculations were performed to study the binding interaction of Zileuton and arachidonic acid with 5-LO. The models with low binding energy were selected for further minimization with AMBER force field.