RNA–lipid interactions directly influence RNA activity, which plays a crucial role in the development of new applications in medicine and biotechnology. However, while specific preferential behaviors between RNA and lipid bilayers have been identified experimentally, their molecular origin remains unexplored. Here we use molecular dynamics simulations to investigate the interaction between RNA and membranes composed of zwitterionic lipids at the atomistic level. Our data reproduce and rationalize previous experimental observations, including that short-chain RNAs rich in guanine have a higher affinity for gel-phase membranes compared to RNA sequences rich in other nucleotides and that RNA prefers gel-phase membranes to fluid bilayers. Our simulations reveal that RNA order is a key molecular determinant of RNA–zwitterionic phospholipid interactions. Our data provide a wealth of information at the atomic level that will help accelerate research on RNA–lipid assemblies for task-specific applications such as designing lipid-based nanocarriers for RNA delivery.

中文翻译：

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RNA 顺序调节其与两性离子脂质双层的相互作用


RNA-脂质相互作用直接影响 RNA 活性，这在医学和生物技术新应用的开发中起着至关重要的作用。然而，虽然已经通过实验确定了 RNA 和脂质双层之间的特定优先行为，但它们的分子起源仍未得到探索。在这里，我们使用分子动力学模拟在原子水平上研究 RNA 与两性离子脂质组成的膜之间的相互作用。我们的数据复制并合理化了以前的实验观察结果，包括与富含其他核苷酸的 RNA 序列相比，富含鸟嘌呤的短链 RNA 对凝胶期膜具有更高的亲和力，并且 RNA 更喜欢凝胶期膜而不是流体双层。我们的模拟表明，RNA 顺序是 RNA-两性离子磷脂相互作用的关键分子决定因素。我们的数据在原子水平上提供了丰富的信息，这将有助于加速 RNA-脂质组装的研究，用于特定任务的应用，例如设计用于 RNA 递送的基于脂质的纳米载体。