Molecular Dynamics Simulation To Investigate The Catalytic Efficiency For Non-specific Substrates Of VmoLac

The widespread use of organophosphorus ester compounds makes organophosphorus residues enrich in the organism through the food chain,which poses a great threat to human health.Looking for a low-cost method to remove organophosphorus residues is imminent.Phosphotriesterase-Like Lactonases（PLLs）are a class of natural lactone enzymes with low phosphotriesterase activity,and are capable of hydrolyzing paraoxon and acyl homoserine lactones.Various lactones.Therefore,it can be used as the target protein of organophosphorus ester pesticide residues.In order to explore the interaction between the PLLs family of enzymes and different substrates,in this work,represented by VmoLac（PLLs-A family）,molecular docking and conventional molecular dynamics simulations were carried out based on the catalytic hydrolysis mechanism of PLLs.From the perspective of protein conformation change and theoretical catalytic mechanism,the catalytic activity of VmoLac non-specific substrate was explored,and the reason why VmoLac had high thermal stability was deeply understood,providing theoretical support for the experimental results.The main results are as follows:Molecular docking results show that the four substrates are bound to the active center of Vmo Lac,the binding of substrates 3-oxo-C10-AHL andγ-nonalactone to VmoLac is stable,and Vmo Lac catalyzes the hydrolysis of 3-oxo-C10-AHL andγ-nonalactone.The ability is stronger.At the same time,through simulation comparison at different temperatures,it can be seen that VmoLac is a thermophilic enzyme,which performs well at high temperatures.Quantum chemistry studies have shown that the substrates 3-oxo-C10-AHL and 3-oxo-C6-AHL have lower Egap values,and theγ-nonalactone and ethyl-paraoxon substrates have lower E_gapap values,which indicates that the reactions involving 3-oxo-C10-AHL andγ-nonalactone are more likely to occur to some extent.Molecular dynamics simulation results show that the Loop domain near the active site of Vmo Lac can well promote the binding of the long chain of lactone（substrate 3-oxo-C10-AHL and substrateγ-nonalactone）to the hydrophobicity of Vmo Lac On the channel,it can be easily combined with the active pocket of VmoLac,which also promotes the hydrolysis of 3-oxo-C10-AHL andγ-nonalactone by VmoLac.The results of covariance and PCA analysis showed that the Loop8 domains in 3-oxo-C10-AHL andγ-nonalactone showed significant positive correlation motion,and the protein structure was the most compact and the combination effect was good.This work provides new ideas for the study of the interaction between four non-specific substrates of VmoLac and VmoLac,as well as new solutions for quickly and efficiently solving the problem of organophosphorus pesticide residues,and for the regulation of quorum sensing by signal molecules.The resulting toxic gene expression provides some theoretical support.The selected molecular dynamics simulation calculation method can well analyze and explain the related problems of protein-ligand interaction,and has important theoretical and practical significance.I look forward to looking for a representative protein-ligand interaction system in future work and studying the protein-ligand interaction mechanism.