Structure, Stiffness and Substates of the Dickerson-Drew Dodecamer.
Structure, Stiffness and Substates of the Dickerson-Drew Dodecamer.
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DOI：
10.1021/ct300671y
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发表时间：
2013
影响因子：
5.5
通讯作者：
Lankas, Filip
中科院分区：
文献类型：
--
作者：
Drsata, Tomas;Perez, Alberto;Orozco, Modesto;Morozov, Alexandre V.;Sponer, Jiri;Lankas, Filip
Dickerson-Drew十二聚体（DD） d-[CGCGAATTCGCG]2是一种典型的B-DNA分子，其序列特异性结构和动力学已被许多实验和计算研究所研究。在这里，我们提出了一个分析基于广泛的原子分子动力学（MD）模拟使用不同的离子条件和水模型的DD性质。将0.6-2.4µs长的MD轨迹与现代晶体学和核磁共振数据进行了比较。在模拟中，双端可以采用不同的碱基配对，从而影响低聚物的结构。BI/BII骨架亚态与碱基对阶梯构象之间的明确关系已被确定，扩展了先前的发现，并揭示了螺旋结构中有趣的多态性。对于给定的端对，碱基对阶跃坐标的分布可以分解为与BI/BII主干态相关的类高斯分量。本文首次报道了硬基力学模型的非局部刚度矩阵，提示中央a束的显著刚度特征。采用Riemann距离和Kullback-Leibler散度对刚度矩阵进行比较。基本结构参数在300 ns内收敛较好，BI/BII种群和刚度矩阵收敛较弱。我们的工作提出了关于DD结构动力学、力学性能以及碱基对和主干构型之间耦合的新发现，包括它们的统计可靠性。该结果也可能对优化DNA的未来力场有用。
The Dickerson–Drew dodecamer (DD) d-[CGCGAATTCGCG]2 is a prototypic B-DNA molecule whose sequence-specific structure and dynamics have been investigated by many experimental and computational studies. Here, we present an analysis of DD properties based on extensive atomistic molecular dynamics (MD) simulations using different ionic conditions and water models. The 0.6–2.4-µs-long MD trajectories are compared to modern crystallographic and NMR data. In the simulations, the duplex ends can adopt an alternative base-pairing, which influences the oligomer structure. A clear relationship between the BI/BII backbone substates and the basepair step conformation has been identified, extending previous findings and exposing an interesting structural polymorphism in the helix. For a given end pairing, distributions of the basepair step coordinates can be decomposed into Gaussian-like components associated with the BI/BII backbone states. The nonlocal stiffness matrices for a rigid-base mechanical model of DD are reported for the first time, suggesting salient stiffness features of the central A-tract. The Riemann distance and Kullback–Leibler divergence are used for stiffness matrix comparison. The basic structural parameters converge very well within 300 ns, convergence of the BI/BII populations and stiffness matrices is less sharp. Our work presents new findings about the DD structural dynamics, mechanical properties, and the coupling between basepair and backbone configurations, including their statistical reliability. The results may also be useful for optimizing future force fields for DNA.
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