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 N⁶-methyladenosine (m⁶A) 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 m⁶A in both syn and anti conformation, which thus opens the way to the use of molecular simulations to investigate the effects of N6 methylations on RNA structural dynamics.

中文翻译：

---

N6-甲基腺苷的分子模拟匹配变性实验

转录后修饰对 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，它们在 RNA 中的应用正在蓬勃发展。^{在这里，我们展示了为常用的 AMBER 力场开发的 N 6} -甲基腺苷 (m ⁶ A)的力场参数集不会重现双链变性实验，特别是不能用于描述成对和非成对状态. 然后，我们使用重新加权技术来获得与可用实验数据匹配的新参数。由此产生的力场可用于正确描述^syn和反构象，从而为使用分子模拟研究 N6 甲基化对 RNA 结构动力学的影响开辟了道路。