Ligand Recognition in Viral RNA Necessitates Rare Conformational Transitions
Ligand Recognition in Viral RNA Necessitates Rare Conformational Transitions
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DOI：
10.1021/acs.jpclett.0c01390
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发表时间：
2020-07-16
影响因子：
5.7
通讯作者：
Vashisth, Harish
中科院分区：
文献类型：
--
作者：
Levintov, Lev;Vashisth, Harish
核糖核酸（RNA）是构象灵活的分子，折叠成三维结构，并在不同的细胞过程中发挥重要作用，以及在许多疾病的发展。因此，RNA已成为开发新型治疗方法的重要靶标。RNA功能背后的生物物理过程通常与罕见的结构转换有关，这些结构转换在配体识别中起关键作用。在这项工作中，我们探测这些很少发生的转换使用非平衡模拟的特征解离的配体分子从HIV-1病毒RNA元件。具体而言，我们观察到碱基翻转罕见事件，配体结合/解结合，并提供了这些转换的机制细节。
Ribonucleic acids (RNAs) are conformationally flexible molecules that fold into three-dimensional structures and play an important role in different cellular processes as well as in the development of many diseases. RNA has therefore become an important target for developing novel therapeutic approaches. The biophysical processes underlying RNA function are often associated with rare structural transitions that play a key role in ligand recognition. In this work, we probe these rarely occurring transitions using nonequilibrium simulations by characterizing the dissociation of a ligand molecule from an HIV-1 viral RNA element. Specifically, we observed base-flipping rare events that are coupled with ligand binding/unbinding and also provided mechanistic details underlying these transitions.