计算机辅助模拟技术在脲酶抑制剂筛选中的应用

Application of Computer Aided Simulation Technology in Screening of Urease Inhibitors

尿素施入土壤后发生快速水解,植物无法有效吸收施入土壤中的养分,造成氮素利用率较低。通过分子对接模拟软件,对脲酶4gy7晶体结构进行处理,经分子动力学优化,分别与尿素、正丁基硫代磷酰三胺(NBPT)、对苯二酚(HQ)、(2-硝基苯基)磷酸三酰胺(2-NPT)、ZINC数据库中的9617个小分子进行分子对接,评价其相互作用关系,筛选潜在的脲酶抑制剂小分子。结果表明:尿素、NBPT、HQ、2-NPT与脲酶的平均结合能依次为30.91、32.92、28.36、18.63 kJ/mol,NBPT的效果较理想;9617个小分子的相互作用分析显示,其中5883个小分子可能与脲酶存在相互作用关系,筛选到35个平均结合能大于55 kJ/mol的潜在脲酶抑制剂。计算机辅助模拟技术为新型脲酶抑制剂的开发提供了新的思路。

Due to the fact that urea is rapidly hydrolyzed after being applied into the soil,plants cannot effectively absorb the nutrients applied into the soil which result in low nitrogen utilization rate.Through molecular docking simulation software,the crystal structure of urease 4gy7 is processed,the molecular dynamics is optimized,the structure is docked with urea,n-butyl phosphorothiotriamide(NBPT),hydroquinone(HQ),(2-nitrophenyl)phosphate triamide(2-NPT),and 9617 small molecules in ZINC database,respectively,to evaluate interaction relationship and screen potential urease inhibitor small molecules.The results show that the average binding energy of urea,NBPT,HQ,2-NPT and urease is 30.91、32.92、28.36 and 18.63 kJ/mol respectively,and the effect of NBPT is ideal.The interaction analysis of 9617 small molecules show that 5883 of them may have interaction with urease,and 35 potential urease inhibitors with average binding energy greater than 55 kJ/mol are screened.Computer aided simulation technology provides a new idea for the development of new urease inhibitors.