Surprisingly, the LTA4H enzyme catalyzes both hydrolase and aminopeptidase functions over fatty acid and peptide substrates utilizing the same active site. In order to obtain deeper insight upon this unique characteristic of the enzyme, a set of MD simulations were performed with WT and mutated enzymesubstrate complex structures. The natural epoxy substrate LTA4 of arachidonic acid pathway, which is converted to LTB4 upon the action of the enzyme, was selected as fatty acid substrate to investigate the hydrolase function of the enzyme. In the other hand, RAR tripeptide that is reported to be the preferred peptide substrate of the enzyme [14] was selected to investigate the aminopeptidase function of the enzyme. The L-LTA4 complex was prepared through the molecular docking methodology whereas L-RAR complex was prepared by copying the 3D coordinates of RAR from the X-ray crystal structure of LTA4 ( Figure 3 ). The representative structure obtained from the MD simulation of LTA4H-apoform was used in preparing both the complex structures to compare the structural changes effectively with no artifacts. From the reported site-directed mutagenesis experiments, three amino acid residues from the catalytic active site of the enzyme were predicted to be very important for the enzymatic activities of the enzyme. These residues include one negatively charged E271 residue from the central catalytic domain and two positively charged R563 and K565 residues from the Cterminal domain. Studies mentioned that mutation of this negatively charged residue to a neutral glutamine (E271Q) has completely abrogated both the catalytic activities of the enzyme. But the crystal structure solved with this mutation (PDB ID: 1H19) could not report any structural or conformational changes causing this drastic change in the catalytic activity [14] . It was also proposed that metal (Zn 2+ ) ion present close to the epoxide moiety of LTA4 acts as a weak Lewis acid to activate and open the epoxide ring. It continued to explain that the E271 located in proximity to Zn 2+ also participates in this acid-induced opening of the epoxide ring of LTA4. It was also reported that E271 acts as the N-terminal recognition point in stabilizing the peptide substrates in terms of aminopeptidase reaction of the enzyme. The positively charged residues R563 and K565 were predicted as the carboxylate recognition sites for both the substrates of the enzyme. All mutations of R563 including R563K, which preserved the positive charge, have resulted in complete loss of catalytic functions of the enzyme. The R563K mutant has shown a significant aminopeptidase activity. All these mutations of R563 leading to tremendous change in enzyme functions did not reveal any structural changes explaining the loss of activities. Especially in epoxide hydrolase reaction, the role of R563 was presumed to position the carboxylate tail of the substrates along the catalytic components of the active site [45] . In terms of aminopeptidase reaction, both the positively charged (R563 and K565) residues help each other in aligning the substrate with the catalytic elements and maintaining the binding strength. The mutations K565A and K565M lacking the positive charge have reduced the aminopeptidase and revealed that this positively charged residue assists R563 in carboxylate recognition in aminopeptidase reaction [27] . Despite of this information over the importance of E271, R563, and R565, the structural changes explaining the catalytic activities of the enzyme are lacking. The results of MD simulations of WT and mutant enzyme-substrate complexes discussed in this study will provide a deeper insight from the structural perspective.