The steered molecular dynamics (SMD), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and free energy perturbation (FEP) methods were used to determine the binding affinity of the L-742,001 inhibitor to the endonuclease domain of the A/H1N1/PA influenza viruses (including wild type (WT) and three mutations I79L, E119D and F105S for both pH1N1 PA and PR8 PA viruses). Calculated results showed that the L-742,001 inhibitor not only binds to the PR8 PAs (1934 A influenza virus) better than to the pH1N1 PAs (2009 A influenza virus) but also more strongly interacts with the WT endonuclease domain than with three mutant variants for both pH1N1 PA and PR8 PA viruses. The binding affinities obtained by the SMD, MM-PBSA and FEP methods attain high correlation with available experimental data. Here the FEP method appears to provide a more accurate determination of the binding affinity than the SMD and MM-PBSA counterparts.

使用操纵分子动力学（SMD），分子力学泊松-玻尔兹曼表面积（MM-PBSA）和自由能扰动（FEP）方法确定L-742,001抑制剂与A / H1N1内切核酸酶结构域的结合亲和力/ PA流感病毒（包括野生型（WT）以及针对pH1N1 PA和PR8 PA病毒的三个突变I79L，E119D和F105S）。计算结果表明，L-742,001抑制剂不仅与PR8 PAs（1934 A流感病毒）的结合比与pH1N1 PAs（2009 A流感病毒）的结合更好，而且与WT核酸内切酶结构域的相互作用比与三种突变体更强pH1N1 PA和PR8 PA病毒。通过SMD，MM-PBSA和FEP方法获得的结合亲和力与可获得的实验数据高度相关。