Elastic Energy Partitioning in DNA Deformation and Binding to Proteins.
Elastic Energy Partitioning in DNA Deformation and Binding to Proteins.
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DOI：
10.1021/acsnano.5b06863
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发表时间：
2016-01
期刊：
影响因子：
17.1
通讯作者：
Xiaojing Teng;W. Hwang
中科院分区：
文献类型：
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作者：
Xiaojing Teng;W. Hwang
我们基于超过0.9-μ的S全原子分子动力学模拟确定的局部弯曲主轴来研究DNA的弹性。计算的有序参数描述了DNA作为弹性棒的运动。在10个可能的二核苷酸步骤中，围绕两个主轴的弯曲是各向异性的，但却是线性弹性的。绕质心轴的扭转与弯曲在很大程度上是解耦的，但DNA在典型的热运动范围之外倾向于过度扭转而不弯曲，这与实验观察到的扭转-拉伸耦合是一致的。计算的二核苷酸步骤的弹性刚性产生了与序列相关的持续长度，这与以前的单分子实验一致，这是通过对DNA进行粗粒度模拟来进一步分析的。由模拟构建的寡聚核苷酸的柔性图也与预计算的二核苷酸步骤的刚性图相匹配。这支持了二核苷酸水平上的碱基对相互作用主要负责DNA弹性的前提。此外，我们还分析了1381个蛋白质-DNA复合体的晶体结构。在大多数结构中，DNA是轻微变形的，扭曲占据了总弹性能量的最高部分。相反，在每二核苷酸步骤的弹性能大于约4.16KBT(KBT：热能)的结构中，主要弯曲成为主导。除了含有高度变形的DNA的结构外，二核苷酸台阶的伸展能量最多占总弹性能量的35%，线弹性破坏的结构除外。这种在不同变形模式之间的划分提供了对DNA构象动力学以及它与其他分子和表面相互作用的定量洞察。
We study the elasticity of DNA based on local principal axes of bending identified from over 0.9-μs all-atom molecular dynamics simulations of DNA oligos. The calculated order parameters describe motion of DNA as an elastic rod. In 10 possible dinucleotide steps, bending about the two principal axes is anisotropic yet linearly elastic. Twist about the centroid axis is largely decoupled from bending, but DNA tends to overtwist for unbending beyond the typical range of thermal motion, which is consistent with experimentally observed twist-stretch coupling. The calculated elastic stiffness of dinucleotide steps yield sequence-dependent persistence lengths consistent with previous single-molecule experiments, which is further analyzed by performing coarse-grained simulations of DNA. Flexibility maps of oligos constructed from simulation also match with those from the precalculated stiffness of dinucleotide steps. These support the premise that base pair interaction at the dinucleotide-level is mainly responsible for the elasticity of DNA. Furthermore, we analyze 1381 crystal structures of protein-DNA complexes. In most structures, DNAs are mildly deformed and twist takes the highest portion of the total elastic energy. By contrast, in structures with the elastic energy per dinucleotide step greater than about 4.16 kBT (kBT: thermal energy), the major bending becomes dominant. The extensional energy of dinucleotide steps takes at most 35% of the total elastic energy except for structures containing highly deformed DNAs where linear elasticity breaks down. Such partitioning between different deformational modes provides quantitative insights into the conformational dynamics of DNA as well as its interaction with other molecules and surfaces.