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运用分子动力学(molecular dynamics,MD)和MM-PBSA(molecular mechanics/Poisson Boltzmann surface area)相结合的方法预测了β-环糊精(cyclodextrin,CD)和甾类客体分子包结模式.通过重原子均方根偏差(root mean square deviation,RMSD)分析可得,两种包结模式下客体分子都可以和β-CD形成稳定的包结.在MD轨迹采样基础上,采用高效MM-PBSA方法计算了两种包结模式下的包结自由能.计算结果显示,β-CD和三个甾类客体分子包结的主要驱动力为范德华相互作用,而溶剂化能和熵变则不利于体系的包结.进一步分析平均构象和包结自由能发现,对于波尼松龙,D-up(D-ring up orientation)取向为优势包结模式;而乙炔雌二醇和雌三醇的优势包结模式均为A-up(A-ring up orientation)取向.通过比较β-CD和三个客体分子的理论包结自由能,预测包结稳定性的次序为乙炔雌二醇>雌三醇>波尼松龙,和实验结果相一致.
The molecular entanglement patterns of β-cyclodextrin (CD) and steroid guest molecules were predicted by a combination of molecular dynamics (MD) and molecular dynamics (Poisson Boltzmann) surface area. According to the analysis of root mean square deviation (RMSD), guest molecules can form stable inclusion with β-CD in both modes of inclusion. On the basis of MD trajectory sampling, high efficiency MM-PBSA method The inclusion entanglement energies of two inclusion modes are calculated.The results show that the main driving force for inclusion of β-CD and three steroid guest molecules is Van der Waal’s interaction, while solvation energy and entropy change are not good for the system .Further analysis of the average conformation and entanglement can find that D-up (D-ring up orientation) orientation is the predominant inclusion mode for prednisolone, whereas the predominant inclusion of ethinyl estradiol and estriol Mode is A-up (A-ring up orientation) orientation. By comparing the theoretical entrapment energies of β-CD and three guest molecules, the order of entrapment stability is predicted as ethinyl estradiol> estriol> wave Nisong Long, consistent with the experimental results.