人参皂苷Rg3立体异构体差异抑制糖尿病调控基因蛋白-PXR机制的分子动力学研究

目的：为进一步了解Rg3对映体的立体化学选择性，对PXR配体结合结构域（PXR ligand-binding domain，PXR-LBD）中20（R/S）-Rg3的结合模式进行建模。方法：使用计算对接，分子动力学（molecular dynamics，MD）和基本动力学分析（essential dynamics analysis，EDA）等技术手段进行建模。结果：PXR中20（S）-Rg3的MM / PB-SA估计结合能大于20（R）-Rg3。两种配合物的RMSFs表明，20（S）-Rg3结合的LBD的迁移率比20（R）型对映体的迁移率降低得多。EDA预测和两个复合物的叠加三维结构都表明20（S）-Rg3在PXR中的结合比20（R）-Rg3更可能与生物学结果一致。结论：以上结果表明，基于目前的模拟结果，PXR中20（S）-Rg3的结合模式比20（R）-Rg3更有可能与生物实验结果吻合。

The molecular dynamics (MD) study on the regulating mechanism of gene protein-PXR of diabetes differentially inhibited by ginsenoside Rg3 stereoisomers

OBJECTIVE To further understand the stereo-chemical selectivity of Rg3 enantiomers by timely establishing the binding modes of 20(R/S)-Rg3 in the hPXR-LBD. METHODS Computational docking, molecular dynamics (MD) and essential dynamics analysis (EDA) were used in this study. RESULTS The results indicated that the MM/PB-SA estimated binding energy of 20(S)-Rg3 in PXR was larger than that of 20(R)-Rg3. The RMSFs of the two complexes indicated that the mobility of the LBD with the binding of 20(S)-Rg3 was reduced much more than that with the 20(R)-form enantiomer. The EDA projections and the superimposed 3D structures of the two complexes both demonstrated that the binding of 20(S)-Rg3 in PXR was more probable than that of 20(R)-Rg3 which agreed with the biological results. CONCLUSION Binding mode of 20(S)-Rg3 in PXR is more probable than that of 20(R)-Rg3 based on current modeling results which well agrees with the biological experimental results.