Starting from the SMILES string, we generated 1000 conformations of paraoxon using OMEGA 3.0.8 (OpenEye Scientific Software) ). Since most previous structural studies assume that the binding orientation of paraoxon is similar to that of the substrate analog ), 4-methylbenzylphosphonate, we chose to perform the docking using three different tools from the OpenEye toolkits to evaluate whether these two compounds share a similar binding mode. These docking tools are: POSIT, HYBRID, and FRED. POSIT matches the 3D shape of a given reference ligand and suggests a single docked pose that has a similar binding orientation as a reference ligand. HYBRID uses a reference crystallographic ligand to guide the docking process. Similar to POSIT, HYBRID uses a ligand-based scoring function that scores similar shape and 3D alignment between the docked ligand and the reference crystallographic structure. However, unlike POSIT, HYBRID uses the conformers of the ligand pre-generated with OMEGA and places them in several orientations in the protein active site. FRED doesn't use a reference ligand and outputs docked poses that complement the active site (McGann 2012). The analog substrate structure, 4-methylbenzylphosphonate, was used as a reference ligand with POSIT and HYBRID. By using POSIT, we aimed to reproduce the binding orientation of 4-methylbenzylphosphonate and evaluate whether this is the correct binding mode of paraoxon, as described in previous studies. HYBRID was used to dock paraoxon with respect to the position of 4-methylbenzylphosphonate in the OPH binding site to suggest binding modes of paraoxon that are close to the binding mode of 4-methylbenzylphosphonate.