MD simulations on each selected docked pose in complex with OPH were carried out using the OpenMM simulation package 7.1.1 ). We assigned partial charges to the substrate (paraoxon) atoms using the AM1-BCC charge model . We used tleap, a tool from the Amber16 package, to generate the water box and parameters. The protein and substrate were parameterized using Amberff14SB and GAFF version 1.8 force fields, respectively. The protein-substrate complex was then solvated using tleap with TIP3P water model in a cubic box with a 10 Å padding. Na + and Cl - counter ions were added to neutralize the system. We used the hydrogen mass repartitioning (HMR) approach with a simulation time step of 4 fs. Long-range electrostatic interactions were calculated using the particle mesh Ewald method ) with a cutoff of 10 Å for the real space electrostatics and Lennard-Jones forces. We minimized the water and ions for 4000 steps, while keeping the protein and the substrate restrained using 500 kcal/mol-Å 2 positional restraints. Then, we performed a second minimization step on the water and ions for 4000 steps, with the protein and the substrate fixed using 50 kcal/mol-Å 2 positional restraints. Next, we heated up the system from 10 K to 300 K in an NVT ensemble for 200 ps, while gradually releasing the restraints on the protein-substrate complex. Also, we kept the positional restraints on the Zn(II) ions belonging to the active site of OPH during the minimization, equilibration and production steps. The temperature was controlled in the NVT simulations through Langevin dynamics with a collision frequency of 1 ps -1 .