Systematic coarse-grained modeling of complexation between small interfering RNA and polycations.
Systematic coarse-grained modeling of complexation between small interfering RNA and polycations.
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DOI：
10.1063/1.4937384
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Zonghui Wei;Erik Luijten
中科院分区：
文献类型：
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作者：
Zonghui Wei;Erik Luijten
全原子分子动力学模拟可以通过阐明聚合物基因传递载体的相互作用和与核酸的详细结合模式，提供对其特性的深入了解。然而，为了探索这些聚合物与核酸络合形成的纳米颗粒，并在实验相关的时间和长度尺度上研究它们的行为，需要一个可靠的粗粒度模型。在这里，我们系统地开发了小干扰RNA （siRNA）和接枝聚乙烯亚胺共聚物络合的模型，这是siRNA递送的一个有希望的候选者。我们将该模型的预测与全原子模拟进行了比较，并证明它能够再现详细的结合模式、电荷特征和水释放动力学。由于粗粒度模型将模拟速度提高了一到两个数量级，因此可以定量研究涉及多个siRNA分子和阳离子共聚物的纳米颗粒形成。
All-atom molecular dynamics simulations can provide insight into the properties of polymeric gene-delivery carriers by elucidating their interactions and detailed binding patterns with nucleic acids. However, to explore nanoparticle formation through complexation of these polymers and nucleic acids and study their behavior at experimentally relevant time and length scales, a reliable coarse-grained model is needed. Here, we systematically develop such a model for the complexation of small interfering RNA (siRNA) and grafted polyethyleneimine copolymers, a promising candidate for siRNA delivery. We compare the predictions of this model with all-atom simulations and demonstrate that it is capable of reproducing detailed binding patterns, charge characteristics, and water release kinetics. Since the coarse-grained model accelerates the simulations by one to two orders of magnitude, it will make it possible to quantitatively investigate nanoparticle formation involving multiple siRNA molecules and cationic copolymers.