羟基化树状大分子与布洛芬相互作用的分子模拟研究

采用分子对接和分子动力学(MD)的模拟方法研究了第四代羟基为末端基团的树状大分子(PAMAM-G4-OH)与布洛芬的相互作用机理并对形成的复合物稳定性进行研究,结果发现:布洛芬插入PAMAM-G4-OH树状大分子空穴,羧基基团靠近核心;对接过程中分子间的范德华力和分子间的氢键贡献很大;将复合物体系进行2000 ps的MD模拟,发现前1000 ps体系的势能、总能量和RMSD值持续下降趋于平衡,最后分别在-1639 kcal/mol～-1701 kcal/mol,-457.009 kcal/mol～-475.809 kcal/mol,0.487A～0.607A范围内波动:复合物的结构起先较松散,经过2000 ps的模拟后逐渐紧凑。结论:树状大分子(PAMAM-G4-OH)与布洛芬主要作用力主为静电力,该静电力主要由布洛芬的羧基去质子化后形成的负电离子和树状大分子内部碱性的叔胺离子产生的;经过2000 ps的分子动力学模拟后,该体系达到了稳定状态。

Molecular simulations on the interaction between hydroxyl-terminated PAMAM dendrimers and ibuprofen

A method based on molecular docking and molecular dynamics(MD) simulations was proposed to investigate the binding mechanism of generation 4 hydroxyl-terminated PAMAM dendrimers(PAMAM-G4-OH) and ibuprofen.The result of molecular docking showed that ibuprofen inserted the cavity of PAMAM-G4-OH with carboxyl group near to the core;van der waal force and hydrogen bond electrostatic force played important roles in process of molecular docking.In addition,during 2000 ps molecular dynamics(MD) simulations, in the first 1000 ps,potential energy,total energy and the value of Root Mean Squared Deviation(RMSD) of the complexation decreased continuingly and finally fluctuated rang from -1639 kcal/mol to -1701 kcal/mol,-457.009 kcal/mol to-475.809 kcal/mol,0.487 to 0.607 A, respectively;Conformation of the complexation was loose at first and became compact gradually.Conclusion:electrostatic force was a major force existed in PAMAM-G4-OH and ibuprofen,which was formed by dendrimer’s internal,basic tertiary amine and ibuprofen’s carboxyl group;the complexation reached to balance after 2000 ps molecular dynamics(MD) simulation.