Abstract

The high dependency and surplus use of agrochemical products have liberated enormous quantities of toxic halogenated pollutants into the environment and threaten the well-being of humankind. Herein, this study performed molecular docking, molecular dynamic (MD) simulations, molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations on the DehH2 from Bacillus thuringiensis, to identify the order of which the enzyme degrades different substrates, haloacids, haloacetate and chlorpyrifos. The study discovered that the DehH2 favored the degradation of haloacids and haloacetates (−3.3 − 4.6 kcal/mol) and formed three hydrogen bonds with Asp125, Arg201 and Lys202. Despite the inconclusive molecular docking result, chlorpyrifos was consistently shown to be the least favored substrate of the DehH2 in MD simulations and MM-PBSA calculations. Results of MD simulations revealed the DehH2-haloacid- (RMSD 0.15 − 0.25 nm) and DehH2-haloacetates (RMSF 0.05 − 0.25 nm) were more stable, with the DehH2-L-2CP complex being the most stable while the least was the DehH2-chlorpyrifos (RMSD 0.295 nm; RMSF 0.05 − 0.59 nm). The Molecular Mechanics Poisson-Boltzmann Surface Area calculations showed the DehH2-L-2CP complex (−24.27 kcal/mol) having the lowest binding energy followed by DehH2-MCA (−22.78 kcal/mol), DehH2-D-2CP (−21.82 kcal/mol), DehH2-3CP (−21.11 kcal/mol), DehH2-2,2-DCP (−18.34 kcal/mol), DehH2-2,3-DCP (−8.34 kcal/mol), DehH2-TCA (−7.62 kcal/mol), while chlorpyrifos was unable to spontaneously bind to DehH2 (+127.16 kcal/mol). In a nutshell, the findings of this study offer valuable insights into the rational tailoring of the DehH2 for expanding its substrate specificity and catalytic activity in the near future.

Communicated by Ramaswamy H. Sarma

摘要

农化产品的高度依赖和过度使用已将大量有毒卤化污染物释放到环境中，威胁着人类的福祉。在此，本研究对苏云金芽孢杆菌的 DehH2 进行了分子对接、分子动力学 (MD) 模拟、分子力学-泊松玻尔兹曼表面积 (MM-PBSA) 计算，以确定酶降解不同底物、卤酸、卤乙酸和毒死蜱的顺序。研究发现，DehH2 有利于卤酸和卤乙酸的降解（-3.3 - 4.6 kcal/mol），并与 Asp125、Arg201 和 Lys202 形成三个氢键。尽管分子对接结果尚无定论，但毒死蜱始终被证明是 MD 模拟和 MM-PBSA 计算中最不受欢迎的 DehH2 底物。MD 模拟结果显示 DehH2-卤酸- (RMSD 0.15 - 0.25 nm) 和 DehH2-卤乙酸 (RMSF 0.05 - 0.25 nm) 更稳定，其中 DehH2-L-2CP 复合物最稳定，而 DehH2 最不稳定-毒死蜱（RMSD 0.295 nm；RMSF 0.05 - 0.59 nm）。分子力学泊松-玻尔兹曼表面积计算显示 DehH2-L-2CP 复合物 (-24. 27 kcal/mol) 具有最低的结合能，其次是 DehH2-MCA (-22.78 kcal/mol)、DehH2-D-2CP (-21.82 kcal/mol)、DehH2-3CP (-21.11 kcal/mol)、DehH2-2 ,2-DCP (-18.34 kcal/mol)、DehH2-2,3-DCP (-8.34 kcal/mol)、DehH2-TCA (-7.62 kcal/mol)，而毒死蜱不能自发结合 DehH2 (+127.16千卡/摩尔）。简而言之，这项研究的结果为合理调整 DehH2 以在不久的将来扩展其底物特异性和催化活性提供了有价值的见解。

由 Ramaswamy H. Sarma 传达