论文标题
N6-甲基腺苷的分子模拟匹配变性实验
Molecular simulations matching denaturation experiments for N6-Methyladenosine
论文作者
论文摘要
转录后修饰对于RNA功能至关重要，并且可能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中的应用正在蓬勃发展。在这里，我们表明，针对常用的琥珀色力场开发的N $^6 $ - 甲基腺苷（M $^6 $ a）的一组力场参数不会重现双链式变性实验，具体来说，不能用来描述配对和不违法的状态。然后，我们使用重新加权技术来得出匹配可用实验数据的新参数。所得力场可用于正确描述SYN和抗构象中的配对和未配对的M $^6 $ A，因此为使用分子模拟的方式开辟了道路，以研究N6甲基化对RNA结构动力学的影响。
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$^6$-methyladenosine (m$^6$A) 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 m$^6$A in both syn and anti conformation, and thus opens the way to the use of molecular simulations to investigate the effects of N6 methylations on RNA structural dynamics.
