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我们能否开发出理想的RNA力场? 从模拟UUCGRNA四旋翼和其他系统中吸取的教训

Vojtěch Mlýnský¹, Petra Kührová^1,2, Martin Pykal²

¹Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 00 Brno, Czech Republic.

Journal of chemical theory and computation

|January 15, 2025

概括

评估RNA力场 (ffs) 对于分子动力学 (MD) 模拟至关重要. 最近三种ffsOL3_CP-gHBfix21,DES-Amber和OL3_R2.7在保持RNA结构方面表现出有希望的结果,其中OL3_CP-gHBfix21提供了最准确的折叠自由能量预测.

科学领域:

计算化学计算化学
结构生物学结构生物学
生物物理学的生物物理.

背景情况:

分子动力学 (MD) 模拟对于研究RNA结构动力学至关重要.
MD模拟的准确性严重依赖于所使用的力场 (ff) 的质量.
现有的RNA力场往往难以准确地表示RNA结构动态和稳定性.

研究的目的:

综合评估广泛使用的对添加和可偏振RNA力场 (ffs).
评估使用UUCG四 (TL) 基准系统选择的ffs的性能.
为了确定可靠的ffs准确的RNA结构动态和折叠自由能量计算.

主要方法:

从NMR结构开始的14-mer UUCG TL的标准MD模拟.
增强采样折叠模拟一个8mer UUCG TL从单链形状开始.
用实验数据计算和比较折叠的自由能量 (ΔG°fold).

主要成果:

大多数测试的ffs未能保持本地UUCG TL结构,偏好了替代形状.
最近三个对添加的ffs (OL3_CP-gHBfix21,DES-Amber,OL3_R2.7) 在长时间内保持了原生结构.
OL3_CP-gHBfix21预测了接近实验值的折叠自由能量,而DES-Amber和OL3_R2.7显示了其他系统的显著偏差和性能问题.

结论:

准确地模拟RNA动态与当前的力场仍然是一个重大挑战.
与DES-Amber和OL3_R2.7相比,OL3_CP-gHBfix21显示了UUCG TL系统的优越性能.
需要进一步开发以创建强大的RNA ffs,适用于各种RNA系统.

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