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

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

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,PXRLBD)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。

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 superimposed3 D 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.