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目的利用分子动力学模拟方法研究黄酮苷元B环不同羟基取代对透膜能力的影响规律,并考察理论方法与实验结果的相关性。方法利用GROMACS程序包,通过附加加速度的分子动力学模拟方法得到5种黄酮苷元在双层脂质膜9个不同位置的轨迹,分析分子透膜过程中的能垒、方向性、氢键、相互作用等参数。结果分子动力学模拟数据与文献报道人结肠腺癌Caco-2细胞实验数据具有良好的相关性(r=0.786 2),分子透过磷脂酰胆碱(DPPC)膜的能垒越小,越有利于药物分子透过生物膜。黄酮苷元透膜难易受静电的影响大于范德华作用的影响,分子在膜内形成氢键能力越强,滞留时间就越长。2′位取代可以增加分子各羟基形成氢键的能力,3′或5′位存在羟基时,与极性层适当的静电排斥作用有利于分子透过极性层。结论 B环不同位置取代对黄酮苷元透膜过程中的氢键形成能力、方向、静电相互作用和能垒都有明显的影响,理论模拟的能垒可以作为预测黄酮类化合物透膜吸收的一个重要指标。
Objective To study the influence of different hydroxyl substitutions of flavonoid aglycone B ring on the membrane permeability by molecular dynamics simulation and to investigate the correlation between theoretical and experimental results. Methods The trajectories of five flavonoid aglycone in nine different positions of bilayer lipid membrane were obtained by GROMACS package with molecular dynamics simulation of acceleration. The energy barrier, orientation, hydrogen bonding, Interaction and other parameters. Results The molecular dynamics simulation data showed good correlation with the experimental data of human colon adenocarcinoma Caco-2 cells reported in the literature (r = 0.786 2). The smaller the energy barrier of the molecule through the phosphatidylcholine (DPPC) membrane, the more Beneficial to drug molecules through the biofilm. Flavonoid glycosaminoglycan permeable membrane is more susceptible to electrostatic effects than Van der Waal’s role in the formation of hydrogen bonds in the membrane the stronger, the longer the residence time. The 2’-substitution can increase the ability of each hydroxyl group to form hydrogen bonds, and the appropriate electrostatic repulsion with the polar layer facilitates the molecules to penetrate the polar layer when the hydroxyl group is present at the 3 ’or 5’ position. Conclusion The substitution of B ring at different positions has significant effect on hydrogen bond formation ability, direction, electrostatic interaction and energy barrier in the process of membrane permeabilization of flavonoid aglycone. The energy barrier of theoretical simulation can be used as a predictor of the absorption of flavonoids through the membrane Important indicators.