化学学报 ›› 2009, Vol. 67 ›› Issue (12): 1318-1324. 上一篇    下一篇

研究论文

β-环糊精和甾类化合物的分子动力学模拟

姚雪霞

  

  1. (南京农业大学工学院 南京 210031)

  • 投稿日期:2008-07-01 修回日期:2008-12-15 发布日期:2009-06-28
  • 通讯作者: 姚雪霞

Molecular Dynamics Simulation on β-Cyclodextrin and Steroids

Yao, Xuexia   

  1. (College of Engineering, Nanjing Agricultural University, Nanjing 210031)
  • Received:2008-07-01 Revised:2008-12-15 Published:2009-06-28
  • Contact: Yao, Xuexia

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.

关键词: MM-PBSA, 分子动力学, β-环糊精, 甾类化合物

The possible binding modes between β-cyclodextrin (β-CD) and steroids were predicted by using molecular dynamics (MD) and MM-PBSA (molecular mechanics/Poisson Boltzmann surface area) methods. The guest molecules with two types of binding modes both form stable complexes with β-CD by heavy atom root mean square deviation (RMSD) analysis. Based on the trajectories from MD simulations, the binding free energies for the two types of binding modes were calculated by using the MM-PBSA method. The computed results show that the main impetus for complexes lies in the van der Waals’ interaction between β-CD and three steroids, but the solvation energy and the entropy change produce adverse effect on the complexes. Through further analyzing the averaged conformations and binding free energies of the β-CD and three steroids, it was found that D-up orientation was the preferential binding mode for prednisolone, whereas A-up orientation was the preferential binding mode for ethinyloestradiol and estriol. By comparing the theoretical binding free energies of β-CD with the three steroids, it was obtained that the stability of the inclusion complexes is ethinyloestradiol>estriol>prednisolone, which is in good agreement with the experimental result.

Key words: MM-PBSA, molecular dynamics, β-cyclodextrin, steroid