Biomolecular engineering of biocatalysts hydrolyzing neurotoxic organophosphates

Novel methods of molecular modeling help solving urgent problems in drug design, directed evolution of biocatalysts and biosensors, and a lot of other research fields. Implementation of such methods to organophosphorus hydrolase being perfect research object that hydrolyzes dangerous neurotoxic organophosphates could intensify development of antidote and protective preparations to treat poisoning. Structures of enzyme-polyelectrolyte complexes (EPCs) based on hexahistidine-tagged organophosphorus hydrolase (His6-OPH) with different biopolymers (various modifications of polyglutamic and polyaspartic acid, as well as hydroxyethyl starch and succinylated gelatin) were simulated at different pH using molecular docking. A number of EPCs with expected “positive” effect on maintaining the maximum level of His6-OPH activity, and some “negative” options were produced, and their catalytic performance was studied. The theoretical results were experimentally confirmed for four of the six “positive” options. EPCs obtained possessed up to 20–40% higher catalytic efficiency in hydrolysis reactions of Paraoxon and Parathion-methyl as compared with that of the native His6-OPH. The results obtained may be a good proof of concept for implementation of molecular docking to calculate model complexes of proteins with (bio)polymers of 6.4–105.5 kg/mol. Also, the approach used here could be interesting as alternative or addition to the directed modifications of enzymes to alter their catalytic characteristics.