The molecular mechanics/Poisson-Boltzmann surface area(MM/PBSA) method has been widely used in predicting the binding affinity among ligands,proteins,and nucleic acids.However,the accuracy of the predicted binding ene...The molecular mechanics/Poisson-Boltzmann surface area(MM/PBSA) method has been widely used in predicting the binding affinity among ligands,proteins,and nucleic acids.However,the accuracy of the predicted binding energy by the standard MM/PBSA is not always good,especially in highly charged systems.In this work,we take the protein-nucleic acid complexes as an example,and showed that the use of screening electrostatic energy(instead of Coulomb electrostatic energy) in molecular mechanics can greatly improve the performance of MM/PBSA.In particular,the Pearson correlation coefficient of dataset Ⅱ in the modified MM/PBSA(i.e.,screening MM/PBSA) is about 0.52,much better than that(<0.33)in the standard MM/PBSA.Further,we also evaluate the effect of solute dielectric constant and salt concentration on the performance of the screening MM/PBSA.The present study highlights the potential power of the screening MM/PBSA for predicting the binding energy in highly charged bio-systems.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11874045 and 11774147)。
文摘The molecular mechanics/Poisson-Boltzmann surface area(MM/PBSA) method has been widely used in predicting the binding affinity among ligands,proteins,and nucleic acids.However,the accuracy of the predicted binding energy by the standard MM/PBSA is not always good,especially in highly charged systems.In this work,we take the protein-nucleic acid complexes as an example,and showed that the use of screening electrostatic energy(instead of Coulomb electrostatic energy) in molecular mechanics can greatly improve the performance of MM/PBSA.In particular,the Pearson correlation coefficient of dataset Ⅱ in the modified MM/PBSA(i.e.,screening MM/PBSA) is about 0.52,much better than that(<0.33)in the standard MM/PBSA.Further,we also evaluate the effect of solute dielectric constant and salt concentration on the performance of the screening MM/PBSA.The present study highlights the potential power of the screening MM/PBSA for predicting the binding energy in highly charged bio-systems.
文摘细胞色素P450(以下简称CYP)与昆虫的抗药性密切相关。本研究运用Auto Dock分子对接技术和分子力学泊松-波尔兹曼表面积法(molecular mechanics Poisson-Boltzmann surface area,MM-PBSA)结合自由能计算方法,分析了甜菜夜蛾CYP9A11与3种杀虫剂结合的作用位点、作用力类型和大小。结果表明:CYP9A11与毒死蜱结合形成两个氢键,有8个氨基酸残基参与形成疏水作用力,二者结合自由能为–3 659.80 k J/mol;CYP9A11与灭多威结合形成5个氢键,有3个氨基酸残基形成疏水作用力,结合自由能为–470.92 k J/mol;CYP9A11中有7个氨基酸残基与氯氰菊酯结合形成疏水作用力,结合自由能为–473.44 k J/mol。范德华力是CYP9A11与毒死蜱结合的主要驱动力,极性溶剂化能是CYP9A11与氯氰菊酯和灭多威结合的主要驱动力,这些结果为阐明甜菜夜蛾CYP9A11与3种杀虫剂的结合机理提供了参考。
