Nerve agents are highly toxic organophosphorus compounds, and the wild-type phosphotriesterase (PTE) enzyme is capable of hydrolyzing these organophosphates but with a low catalytic efficiency. Here the whole enzymatic detoxification process of the G-type nerve agent sarin by the PTE enzyme, including the substrate delivery, the chemical reaction, and the product release, has been explored by extensive QM/MM MD and MM MD simulations. The plausible mechanisms for the chemical and nonchemical steps, the roles of water molecules, and the key residues have been discussed. The enzymatic P–F cleavage of sarin is a two-step exothermic process with the free-energy span of 12.3 kcal/mol, and it should be facile in the whole enzymatic catalysis. On the contrary, the initial degraded product is tightly bound to the binuclear zinc center, and its dissociation experiences multiple chemical steps with the free-energy barriers of 21.0 kcal/mol for the recombination process and 18.3 kcal/mol for the release of the product phosphoester from the active site. Notably, the solvation of hydrophilic products in the bulk water is generally exothermic, which provides the driving force for the release of products from the active site. The side-chain residues Leu271 and Phe132 in the transportation channel function as the entrance gate in PTE and play an important gate-switching role to manipulate the substrate access to the active site and the product release. These mechanistic details for the enzymatic degradation of sarin by PTE provide significant clues to improve its activity toward the nerve agents.

The efficient immobilization of haloalkane dehalogenase (DhaA) on carriers with retaining of its catalytic activity is essential for its application in environmental remediation. In this work, adsorption orientation and conformation of DhaA on different functional surfaces were investigated by computer simulations; meanwhile, the mechanism of varying the catalytic activity was also probed. The corresponding experiments were then carried out to verify the simulation results. (The simulations of DhaA on SAMs provided parallel insights into DhaA adsorption in carriers. Then, the theory-guided experiments were carried out to screen the best surface functional groups for DhaA immobilization.) The electrostatic interaction was considered as the main impact factor for the regulation of enzyme orientation, conformation, and enzyme bioactivity during DhaA adsorption. The synergy of overall conformation, enzyme substrate tunnel structural parameters, and distance between catalytic active sites and surfaces codetermined the catalytic activity of DhaA. Specifically, it was found that the positively charged surface with suitable surface charge density was helpful for the adsorption of DhaA and retaining its conformation and catalytic activity and was favorable for higher enzymatic catalysis efficiency in haloalkane decomposition and environmental remediation. The neutral, negatively charged surfaces and positively charged surfaces with high surface charge density always caused relatively larger DhaA conformation change and decreased catalytic activity. This study develops a strategy using a combination of simulation and experiment, which can be essential for guiding the rational design of the functionalization of carriers for enzyme adsorption, and provides a practical tool to rationally screen functional groups for the optimization of adsorbed enzyme functions on carriers. More importantly, the strategy is general and can be applied to control behaviors of different enzymes on functional carrier materials.

Chemical protective clothing (CPC) is major equipment to protect human skin from hazardous chemical warfare agents (CWAs), especially nerve agents and blister agents. CPC performance is mainly dominated by the chemical protective material, which needs to meet various requirements, such as mechanical robustness, protective properties, physiological comfort, cost-effectiveness, and dimensional stability. In this study, polyvinylidene fluoride (PVDF) based sodium sulfonate membranes with different ion exchange capacities (IECs) are prepared simply from low-cost materials. Their mechanical properties, contact angles, permeations, and selectivities have been tested and compared with each other. Results show that membranes with IEC in the range of 1.5–2 mmol g−1 have high selectivities of water vapor permeation over CWA simulant vapor permeation and good mechanical properties. Therefore, PVDF-based sodium sulfonate membranes are potential materials for CPC applications.

Electrostatically driven enzyme orientation leads to different enzyme activities and electron transfer rates on different charged surfaces.

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