Department of Chemical Engineering, University of New Hampshire, Durham 03824, New Hampshire, United States.
J Phys Chem Lett. 2020 Jul 16;11(14):5426-5432. doi: 10.1021/acs.jpclett.0c01390. Epub 2020 Jun 25.
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.
核糖核酸（RNAs）是构象灵活的分子，它们折叠成三维结构，在不同的细胞过程以及许多疾病的发展中发挥着重要作用。因此，RNA 已成为开发新型治疗方法的重要目标。RNA 功能的生物物理过程通常与稀有结构转变有关，这些转变在配体识别中起着关键作用。在这项工作中，我们通过对 HIV-1 病毒 RNA 元件中配体分子的解离进行非平衡模拟来探测这些罕见的转变。具体来说，我们观察到了与配体结合/解吸偶联的碱基翻转稀有事件，并提供了这些转变背后的机制细节。
