Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA.
Department of Physics, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA.
Genes (Basel). 2022 Mar 18;13(3):540. doi: 10.3390/genes13030540.
RNA is critical to a broad spectrum of biological and viral processes. This functional diversity is a result of their dynamic nature; the variety of three-dimensional structures that they can fold into; and a host of post-transcriptional chemical modifications. While there are many experimental techniques to study the structural dynamics of biomolecules, molecular dynamics simulations (MDS) play a significant role in complementing experimental data and providing mechanistic insights. The accuracy of the results obtained from MDS is determined by the underlying physical models i.e., the force-fields, that steer the simulations. Though RNA force-fields have received a lot of attention in the last decade, they still lag compared to their protein counterparts. The chemical diversity imparted by the RNA modifications adds another layer of complexity to an already challenging problem. Insight into the effect of RNA modifications upon RNA folding and dynamics is lacking due to the insufficiency or absence of relevant experimental data. This review provides an overview of the state of MDS of modified RNA, focusing on the challenges in parameterization of RNA modifications as well as insights into relevant reference experiments necessary for their calibration.
RNA 在广泛的生物和病毒过程中至关重要。这种功能多样性是其动态性质的结果；它们可以折叠成的各种三维结构；以及一系列转录后化学修饰。虽然有许多实验技术可用于研究生物分子的结构动力学，但分子动力学模拟 (MDS) 在补充实验数据和提供机制见解方面发挥着重要作用。MDS 获得的结果的准确性取决于指导模拟的基础物理模型，即力场。尽管在过去十年中，RNA 力场受到了很多关注，但与蛋白质相比，它们仍然落后。RNA 修饰赋予的化学多样性为已经具有挑战性的问题增加了另一层复杂性。由于缺乏相关的实验数据，因此缺乏对 RNA 修饰对 RNA 折叠和动力学影响的了解。本文综述了修饰 RNA 的 MDS 状态，重点介绍了 RNA 修饰参数化的挑战，以及对其校准所需的相关参考实验的见解。
