Observation of the A-DNA to B-DNA transition during unrestrained molecular dynamics in aqueous solution.
Observation of the A-DNA to B-DNA transition during unrestrained molecular dynamics in aqueous solution.
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DOI：
10.1006/jmbi.1996.0330
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发表时间：
1996-06
影响因子：
5.6
通讯作者：
T. Cheatham;Peter A. Kollman
中科院分区：
文献类型：
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作者：
T. Cheatham;Peter A. Kollman
蛋白质和核酸的分子动力学 (MD) 模拟中的一大挑战是，当在距离很远的地方开始模拟时，找到正确的“实验”几何形状。在这项研究中，我们在 DNA 双链体 d(CCAACGTTGG)2 的水溶液中进行了四个不受限制的大约 1 ns 长度的 MD 轨迹，两个从典型的 A-DNA 结构开始，两个从典型的 B-DNA 结构开始。根据均方根坐标偏差判断，从所有四个轨迹计算出的平均结构彼此收敛在约 0.8 至 1.6 埃（所有原子）内，这与为该序列报告的 B-DNA 样 X 射线结构相距 1.3 至 1.7 埃（每条链中央六个残基的所有原子）和 3.1 至 3.6 埃（所有原子）。据我们所知，这是多纳秒分子动力学轨迹的第一个例子，完全代表了 DNA 电荷、溶剂和长程静电，证明了内部一致性（两种不同的起始结构和四种不同的轨迹导致一致的平均结构），并且与该序列的 X 射线晶体结构和水溶液中双链 DNA 的 NMR 数据相当一致。给定序列结构的这种内部一致性表明，人们现在可以开始使用分子动力学来实际检查 DNA 双链体中序列依赖性结构效应。
A large challenge in molecular dynamics (MD) simulations of proteins and nucleic acids is to find the correct "experimental" geometry when a simulation is started a significant distance away from it. In this study, we have carried out four unrestrained approximately 1 ns length MD trajectories in aqueous solution on the DNA duplex d(CCAACGTTGG)2, two beginning in a canonical A-DNA structure and two beginning in a canonical B-DNA structure. As judged by root-mean-squared coordinate deviations, average structures computed from all four of the trajectories converge to within approximately 0.8 to 1.6 angstroms (all atoms) of each other, which is 1.3 to 1.7 angstroms (all atoms of the central six residues from each strand) and 3.1 to 3.6 angstroms (all atoms) away from the B-DNA-like X-ray structure reported for this sequence. To our knowledge, this is the first example of multiple nanosecond molecular dynamics trajectories with full representation of DNA charges, solvent and long range electrostatics that demonstrate both internal consistency (two different starting structures and four different trajectories lead to a consistent average structure) and considerable agreement with the X-ray crystal structure of this sequence and NMR data on duplex DNA in aqueous solution. This internal consistency of structure for a given sequence suggests that one can now begin to realistically examine sequence-dependent structural effects in DNA duplexes using molecular dynamics.