β-环糊精包合阿德福韦的理论研究

Theoretical studies on the inclusion complexes of PMEA and β-cyclodextrin

目的采用计算机辅助模拟设计对环糊精的包合作用进行理论研究,从分子水平对β-环糊精(β-CD)包合阿德福韦(PMEA)的可行性进行研究和探讨。方法受体β-CD结构取自剑桥晶体结构库中"HEGXUM"的晶体复合物,不同价态的配体PMEA在OPLAS2005分子力场下经过优化后,以对接方法研究包合作用。结果在包合过程中,PMEA容易被β-CD包合,包合后容易形成PMEA-β-CD包合物;包合过程中以β-CD:PMEA=2:1包合较β-CD:PMEA=1:1包合更容易形成包合物;分子间的范德华作用能起主要作用,而静电作用能起次要作用;配体PMEA所带的价电荷数也会对包合作用产生影响,PMEA在中性或带正电时可能有利于β-CD单分子包合,带负电荷有利于双分子β-CD包合。结论β-CD与PMEA容易形成PMEA-β-CD包合物,包合的模式受β-CD摩尔比例和PMEA的带电状态的影响。

Objective Using the method of assistant simulation deesign by computer to investigate the rules of forming inclusion complexes between cyclodextrin （β-CD） and adefovir （PMEA） from the molecu- lar level. Methods The structures of β-CD were from the crystalline structure （HEGXUM）. The struc-tures of PMEA with different charges were optimized under OPLAS2005 force field. The inclusion complexes were simulated by docking method of Glide in Schrodinger software package. Results PMEA and β-CD easy to form the PMEA-β-CD inclusion complex. The 2 parts of β-CD are more easily to form the inclusion complex with than PMEA than one part. Among the total energy, Van der Waals energy play a major role compared with the electrostatic interaction. The different charges states can change the models of inclusion. The positive PMEA favors mono β-CD, and the negative PMEA prefers β-CD dimmer. Conclusion β-CD and PMEA can easy to form the inclusion complex. The portion of β-CD and the charges states of PMEA have effects on the models of inclusion complexes.