化学物质在核酸骨干中的转移来自于分子动力学和密度函数计算的结合
Jana Přecechtělová1, Petr Novák, Markéta L Munzarová
1National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kotlářská 2, CZ-61137 Brno, Czech Republic.
量子化学分析显示,骨干扭转角度显著影响DNA中的-31化学转移. 这些发现与实验数据一致,改善了我们对DNA结构和动态的理解.
科学领域:
- * 生物物理化学 生物物理化学
- * 计算化学 计算机化学
- * 分子生物学 * 分子生物学
背景情况:
- *-31 ((31) P) 化学变化是DNA结构和动态的敏感探针.
- *了解DNA骨干扭转角度和 (31) P化学转移之间的关系对于解释NMR数据至关重要.
- *以前的研究已经表明了联系,但缺乏全面的量子化学分析.
研究的目的:
- *对DNA骨干扭曲角度如何影响 (31) P化学转移进行详细的量子化学调查.
- *根据分子动力学模拟,使用水合二甲基酸盐来建模二链.
- * 将计算预测与实验核磁共振 (NMR) 数据进行比较.
主要方法:
- *使用密度函数理论 (DFT) 的计算.
- *从DNA分解器的分子动力学 (MD) 模拟中的快照[d(CGCGAATTCGCG) ]2被用于生成模型几何形状.
- * 一个水合二甲基酸盐分子作为二结合的模型.
主要成果:
- * DFT计算准确地复制了B (I) 和B (II) DNA形状之间的 (31) P化学转移中的实验差异 (2.1 ± 0.3 ppm和1.6 ± 0.3 ppm与1.6 ppm实验).
- *与混合的B(I) /B(II) 状态相比,对于纯的B(I) DNA残留物观察到更负的 (31) P化学转移,与NMR发现一致.
- *在B (I) (3.5 ± 0.8 ppm) 和B (II) (4.5 ± 1.5 ppm) 两个区域都发现了 (31) P化学转移中的显著分散.
- *扭转角α和 ζ被确定为 (31) P化学转移的主要驱动因素,隐式溶剂模型足以满足β和ε.
- *明确的溶剂处理导致了2-3ppm的上场转移和扭转角度依赖性的减缓.
结论:
- * 脊柱扭转角度,特别是α和 ζ,在确定DNA中的 (31) P化学转移方面发挥着主导作用.
- * 计算模型与实验性NMR数据提供了很好的一致性,验证了它的实用性.
- *这项研究强调了 (31) P 化学转移在不同 DNA 构造状态中的实质性变异性.
- *明确的溶剂效应对于准确预测 (31) P化学转移及其扭矩角度依赖性很重要.
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