Joint IRB-BSC Program on Computational Biology, Institute for Research in Biomedicine, Parc Cientific de Barcelona, Josep Samitier 1-5, Barcelona 08028, Spain.
Nucleic Acids Res. 2012 Nov;40(21):10668-78. doi: 10.1093/nar/gks884. Epub 2012 Sep 24.
The traditional mesoscopic paradigm represents DNA as a series of base-pair steps whose energy response to equilibrium perturbations is elastic, with harmonic oscillations (defining local stiffness) around a single equilibrium conformation. In addition, base sequence effects are often analysed as a succession of independent XpY base-pair steps (i.e. a nearest-neighbour (NN) model with only 10 unique cases). Unfortunately, recent massive simulations carried out by the ABC consortium suggest that the real picture of DNA flexibility may be much more complex. The paradigm of DNA flexibility therefore needs to be revisited. In this article, we explore in detail one of the most obvious violations of the elastic NN model of flexibility: the bimodal distributions of some helical parameters. We perform here an in-depth statistical analysis of a very large set of MD trajectories and also of experimental structures, which lead to very solid evidence of bimodality. We then suggest ways to improve mesoscopic models to account for this deviation from the elastic regime.
传统的介观范例将 DNA 表示为一系列碱基对步骤，其对平衡扰动的能量响应是弹性的，围绕单个平衡构象进行谐波振荡（定义局部刚度）。此外，碱基序列效应通常被分析为一系列独立的 XpY 碱基对步骤（即只有 10 种独特情况的最近邻 (NN) 模型）。不幸的是，ABC 联盟最近进行的大规模模拟表明，DNA 灵活性的真实情况可能要复杂得多。因此，需要重新审视 DNA 灵活性范例。在本文中，我们详细探讨了灵活性的弹性 NN 模型最明显的违反之一：一些螺旋参数的双峰分布。我们在这里对非常大量的 MD 轨迹和实验结构进行了深入的统计分析，得出了双峰的非常可靠的证据。然后，我们提出了改进介观模型的方法，以解释这种偏离弹性状态的情况。
