分子动力学模拟己二胺为核的树形分子与生物膜相互作用  

Molecular dynamics simulation of dendrimer with diaminohexane as interior core interacting with biomembrane

作　　者：屠晨坤[1] TU Chenkun(Kangda College,Nanjing Medical University,Lianyungang 222006,Jiangsu,China)

机构地区：[1]南京医科大学康达学院

出　　处：《计算机与应用化学》2019年第4期312-318,共7页Computers and Applied Chemistry

基　　金：国家自然科学基金青年基金资助项目(11804244);江苏省南京医科大学康达学院科研发展基金资助(KD2017KYJJYB005)

摘　　要：研究树形分子与生物膜间相互作用对于理解药物输运和基因转染是非常有帮助的。为了考察两者间的作用机制,更好的理解药物输运过程,本文采用粗粒化分子动力学方法来研究在酸性和中性条件下,以己二胺(DAH)为核的第四代树形分子(以下简称为DAH型树形分子)单独在水溶液中的结构变化以及其与生物膜作用行为。相比较乙二胺(EDA)为核心的树形分子,DAH型树形分子封装能力强、具有更大的内部空间。发现在中性条件下,DAH型树形分子有折叠现象,一定程度阻碍了水分子进入DAH型树形分子内部;在酸性条件下,折叠现象不明显,DAH型树形分子回旋半径变大,内部容纳更多的水分子。与膜作用后,中性条件的DAH型树形分子吸附在生物膜外表面;随着pH值下降,由于静电吸引作用,DAH型树形分子嵌入了带负电的生物膜中,非对称生物膜内表面带负电的脂质分子翻转至外表面,使得生物膜厚度变薄并发生穿膜现象,甚至产生了孔洞。Studying dendrimer interacting with biomembrane is important for understanding drug delivery and gene transfection. Here the coarse-grained molecular dynamics simulations are performed to investigate the behaviors of polyamidoamine(PAMAM) dendrimer(G4) with diaminohexane(DAH) as interior core interacting with biomembranes at different pHs. Comparing with the traditional PAMAM(ethylenediamine core), PAMAM with the DAH core shows higher inner cavities and improves encapsulation efficiency. And the smaller number of water beads can penetrated into the inner cavities in physiological environment. However, PAMAM with the DAH core reduces the amount of back-folded terminals and creates more cavities to accommodate water beads in acidic environment. During the interaction with the asymmetric membrane, the radius of gyration of the PAMAM with the DAH core increases both in acidic environment and physiological environment. DAH-dendrimer only adsorbs onto the membrane at the physiological environment, leading to the deformation of the membrane. However, in the acidic environment, it is found that the monomers of DAH-dendrimer pass through the bilayer to contact with the electronegative lipids in the opposite leaflet of the asymmetrical bilayer. The introduction of DAH-dendrimer may cause local membrane thinning even pore formation, which improves the membrane permeability.

关 键 词：分子核心 生物膜 药物载体 相互作用 分子动力学模拟 

分 类 号：TQ015.9[化学工程] TP391.9[自动化与计算机技术—计算机应用技术]