  A combined molecular docking and molecular structure in silico analysis on
the substrate and product of leukotriene A4 hydrolase (LTA4H) was performed.
The molecular structures of the substrate leukotriene A4 (LTA4) and product
leukotirene B4 (LTB4) were studied through Density Functional Theory (DFT)
calculations at the B3LYP/6-31+G(d) level of theory in both, gas and condensed
phases. The whole LTB4 molecule was divided into three fragments (hydrophobic
tail, triene motif, and a polar acidic group) which were subjected to a full
conformational study employing the most stable conformations of them to build
conformers of the complete molecule and geometry optimize further. LTA4
conformers structures were modeled from the LTB4 minimum energy conformers.
Both, protonated and deprotonated species of LTA4 and LTB4, were analyzed
according to pKa values founded in the literature. Finally, a binding model of
LTA4 with LTA4 hydrolase is proposed according to docking results which show
intermolecular interactions that position the protonated and deprotonated
ligand in the active site, in excellent agreement with experimental data.
