Poly(amidoamine)-based Dendrimer/siRNA Complexation Studied by Computer Simulations: Effects of pH and Generation on Dendrimer Structure and siRNA Binding
Poly(amidoamine)-based Dendrimer/siRNA Complexation Studied by Computer Simulations: Effects of pH and Generation on Dendrimer Structure and siRNA Binding
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DOI：
10.1002/mabi.201100276
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发表时间：
2012-02-01
影响因子：
4.6
通讯作者：
Pricl, Sabrina
中科院分区：
文献类型：
--
作者：
Karatasos, Kostas;Posocco, Paola;Pricl, Sabrina
在这项工作中，我们报告，比较和讨论从完全原子分子动力学模拟的第4代，第5代和第6代的PAMAM为基础的树枝状聚合物具有NH3和三乙醇胺为核心，形成复合物与短干扰RNA（siRNA）在不同的pH值和生理离子强度。通过采用详细的分析，我们展示了如何功能，如分子大小，结构的细节，这一类的树枝状聚合物的质子化水平影响的树枝状聚合物/siRNA复合。树枝状聚合物的构象灵活性，组装的有效电荷分布，以及两个分子实体之间的分子内和分子间氢键的水平等性质都被发现在核酸和超支化分子之间的相互作用中发挥重要作用。所有这些特征在树状聚合物/基因复合的多方面机制中具有关键重要性，并且它们的理解可以为设计更有效的核酸纳米载体提供有价值的见解。
In this work we report, compare and discuss the results obtained from fully atomistic molecular dynamics simulations of generations 4, 5, and 6 of PAMAM-based dendrimers having NH3 and triethanolamine as cores, forming complexes with a short interfering RNA (siRNA) at different pH values and at physiological ionic strength. By employing a detailed analysis we demonstrate how features such as molecular size, structural details, and protonation level of this category of dendrimers affect the dendrimer/siRNA complexation. Properties like the conformational flexibility of the dendrimer, the effective charge distribution of the assembly, and the level of intra- and intermolecular hydrogen bonding between the two molecular entities are all found to play a significant role in the mutual interactions between the nucleic acid and the hyperbranched molecules. All these features are of key importance in the multifaceted mechanism of dendrimer/gene complexation, and their understanding can provide valuable insight toward the design of more efficient nucleic acid nanocarriers.