<br>通过分子动力学模拟揭示 PEI/DNA 和 PEI/siRNA 复合物的结构比较,The Journal of Physical Chemistry B

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通过分子动力学模拟揭示 PEI/DNA 和 PEI/siRNA 复合物的结构比较
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2017-02-14 00:00:00 , DOI: 10.1021/acs.jpcb.6b10775
Jesse D Ziebarth ₁ , Dennis R Kennetz ₁ , Nyles J Walker ₁ , Yongmei Wang ₁

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由聚乙烯亚胺（PEI）和DNA或siRNA组成的聚合复合物因其在基因治疗中的应用而引起了极大的关注。尽管这些复合物的许多物理化学特性仍然未知，但 PEI/DNA 复合物已被反复证明比其 PEI/siRNA 对应物更稳定。在这里，我们使用线性 PEI 和含有相同碱基数的 DNA 或 siRNA 双链体之间的络合原子分子动力学模拟来检查这种差异的潜在原因。这两种类型的复合物通过相似的相互作用来稳定，因为PEI胺主要与核酸磷酸基团相互作用，但偶尔也与两种核酸的凹槽原子相互作用。然而，PEI/DNA 复合物中的相互作用数量比同类 PEI/siRNA 复合物要多，其中质子化 PEI 胺与 DNA 之间的相互作用尤其增强。这些结果表明 DNA 和 siRNA 之间的结构差异可能在提高 PEI/DNA 复合物稳定性方面发挥作用。此外，我们还研究了 PEI 链与带净正电荷的聚合复合物的结合。 PEI 与这些过度充电的复合物的结合涉及 PEI 与核酸表面上保持负静电势的区域之间的相互作用，并通过从核酸中释放水来促进。

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Structural Comparisons of PEI/DNA and PEI/siRNA Complexes Revealed with Molecular Dynamics Simulations

Polyplexes composed of polyethyleneimine (PEI) and DNA or siRNA have attracted great attention for their use in gene therapy. Although many physicochemical characteristics of these polyplexes remain unknown, PEI/DNA complexes have been repeatedly shown to be more stable than their PEI/siRNA counterparts. Here, we examine potential causes for this difference using atomistic molecular dynamics simulations of complexation between linear PEI and DNA or siRNA duplexes containing the same number of bases. The two types of polyplexes are stabilized by similar interactions, as PEI amines primarily interact with nucleic acid phosphate groups but also occasionally interact with groove atoms of both nucleic acids. However, the number of interactions in PEI/DNA complexes is greater than in comparable PEI/siRNA complexes, with interactions between protonated PEI amines and DNA being particularly enhanced. These results indicate that structural differences between DNA and siRNA may play a role in the increased stability of PEI/DNA complexes. In addition, we investigate the binding of PEI chains to polyplexes that have a net positive charge. The binding of PEI to these overcharged complexes involves interactions between PEI and areas on the nucleic acid surface that have maintained a negative electrostatic potential and is facilitated by the release of water from the nucleic acid.

更新日期：2017-02-14

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