Enhancement of the Activity of Organophosphorus Hydrolase (OPH): An in Silico Approach using Docking, Molecular Dynamics Simulation, and MM-PBSA

Enzymatic detoxification of Organophosphorus (OP) compounds such as nerve agents and some pesticides using enzymes is an ideal and promising approach to address environmental risks. Therefore, producing enzymes with high catalytic activity is necessary to degrade OP compounds. In this study, in silico methods have been studied to assess the effect of mutations in 176 and 184 residues of Brevundimonas diminuta Organophosphorus Hydrolase (OPH) in interaction with paraoxon. According to the molecular docking results, the binding affinity of the native enzymes, A176V, and L184M for paraoxon was -4.57, -4.6, and -4.6kcal/mol, respectively. Likewise, the hydrogen bond was formed in all three complexes between paraoxon and His 257. The 100ns Molecular Dynamic (MD) simulation study showed that the induced mutations have no negative effects on the protein structure's stability, folding, and flexibility. However, RMSF results indicate the possibility of strong and appropriate interactions between the ligand and some of the residues in mutant enzymes. Based on the Molecular-Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) study, it was found that the higher free-binding energy (ΔGbind) was related to L184M, A176V, and native complexes, respectively; thus, L184M and A176V mutations increased the affinity of OPH to paraoxon. Among the energy components, the greatest effect on binding energy is related to polar solvation energy. The results of this computational study can be useful in the production of engineered OPH to increase catalytic efficiency and affinity to paraoxon.