From rigid base pairs to semiflexible polymers: Coarse-graining DNA
From rigid base pairs to semiflexible polymers: Coarse-graining DNA
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DOI：
10.1103/physreve.76.021923
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发表时间：
2007-08-01
影响因子：
2.4
通讯作者：
Everaers, Ralf
中科院分区：
文献类型：
--
作者：
Becker, Nils B.;Everaers, Ralf
刚性碱基对模型详细捕捉了纳米长度尺度上双螺旋 DNA 的弹性，其构象变量是相邻碱基对的相对位置和方向。相应的序列相关弹性势已从全原子MD模拟和高分辨率结构数据中获得。在 100 nm 尺度上，DNA 被成功地通过具有均匀弹性特性的连续蠕虫链模型描述，其特征在于单分子实验中测量的一组四个弹性常数。我们在这里提出了一种理论，通过系统地将刚性碱基对模型粗粒度化为有效的蠕虫状链描述，将不同尺度的这些实验联系起来。准确地考虑了分子的平均螺旋几何形状，并考虑了重复序列和随机序列。结构无序被证明会对热构象波动以及熵弹性产生小的、附加的和短程的校正。我们还讨论了均匀蠕虫链在短尺度上的适用性限制，量化了弯曲刚度的各向异性、非高斯弯曲角度分布和刚度的变化，所有这些在螺旋转弯下都很明显。粗粒弹性参数与实验蠕虫链刚度表现出显着的整体一致性。为了获得最佳匹配潜力，二核苷酸重复的弯曲持久长度范围为 37-53 nm，随机 DNA 值为 43 nm。虽然扭转刚度被低估，拉伸刚度被高估，但违反直觉的负号和扭转-拉伸耦合的大小与最近的实验结果一致。
The elasticity of double-helical DNA on a nm length scale is captured in detail by the rigid base-pair model, whose conformation variables are the relative positions and orientations of adjacent base pairs. Corresponding sequence-dependent elastic potentials have been obtained from all-atom MD simulation and from high-resolution structural data. On the scale of 100 nm, DNA is successfully described by a continuous wormlike chain model with homogeneous elastic properties, characterized by a set of four elastic constants which have been measured in single-molecule experiments. We present here a theory that links these experiments on different scales, by systematically coarse-graining the rigid base-pair model to an effective wormlike chain description. The average helical geometry of the molecule is accounted for exactly, and repetitive as well as random sequences are considered. Structural disorder is shown to produce a small, additive and short-range correction to thermal conformation fluctuations as well as to entropic elasticity. We also discuss the limits of applicability of the homogeneous wormlike chain on short scales, quantifying the anisotropy of bending stiffness, the non-Gaussian bend angle distribution and the variability of stiffness, all of which are noticeable below a helical turn. The coarse-grained elastic parameters show remarkable overall agreement with experimental wormlike chain stiffness. For the best-matching potential, bending persistence lengths of dinucleotide repeats span a range of 37-53 nm, with a random DNA value of 43 nm. While twist stiffness is somewhat underestimated and stretch stiffness is overestimated, the counterintuitive negative sign and the magnitude of the twist-stretch coupling agree with recent experimental findings.