Piomponi Valerio, Fröhlking Thorben, Bernetti Mattia, Bussi Giovanni
Scuola Internazionale Superiore di Studi Avanzati, SISSA, via Bonomea 265, 34136 Trieste, Italy.
ACS Cent Sci. 2022 Aug 24;8(8):1218-1228. doi: 10.1021/acscentsci.2c00565. Epub 2022 Aug 3.
Post-transcriptional modifications are crucial for RNA function and can affect its structure and dynamics. Force-field-based classical molecular dynamics simulations are a fundamental tool to characterize biomolecular dynamics, and their application to RNA is flourishing. Here, we show that the set of force-field parameters for N-methyladenosine (mA) developed for the commonly used AMBER force field does not reproduce duplex denaturation experiments and, specifically, cannot be used to describe both paired and unpaired states. Then, we use reweighting techniques to derive new parameters matching available experimental data. The resulting force field can be used to properly describe paired and unpaired mA in both and conformation, which thus opens the way to the use of molecular simulations to investigate the effects of N6 methylations on RNA structural dynamics.
转录后修饰对于RNA功能至关重要，并且会影响其结构和动力学。基于力场的经典分子动力学模拟是表征生物分子动力学的基本工具，其在RNA上的应用正在蓬勃发展。在此，我们表明，为常用的AMBER力场开发的N-甲基腺苷（mA）的力场参数集无法重现双链变性实验，具体而言，不能用于描述配对和未配对状态。然后，我们使用重加权技术来推导与现有实验数据匹配的新参数。所得的力场可用于恰当地描述处于两种构象的配对和未配对mA，从而为利用分子模拟研究N6甲基化对RNA结构动力学的影响开辟了道路。
