Biophysics Graduate Group, University of California, Berkeley, California 94720, USA.
J Chem Phys. 2012 Jan 28;136(4):045102. doi: 10.1063/1.3679654.
The wormlike chain model of DNA bending accurately reproduces single-molecule force-extension profiles of long (kilobase) chains. These bending statistics over large scales do not, however, establish a unique microscopic model for elasticity at the 1-10 basepair (bp) scale, which holds particular interest in biological contexts. Here, we examine a class of microscopic models which allow for disruption of base pairing (i.e., a "melt" or "kink", generically an "excitation") and consequently enhanced local flexibility. We first analyze the effect on the excitation free energy of integrating out the spatial degrees of freedom in a wormlike chain. Based on this analysis, we present a formulation of these models that ensures consistency with the well-established thermodynamics of melting in long chains. Using a new method to calculate cyclization statistics of short chains from enhanced-sampling Monte Carlo simulations, we compute J-factors of a meltable wormlike chain over a broad range of chain lengths, including very short molecules (30 bp) that have not yet been explored experimentally. For chains longer than about 120 bp, including most molecules studied to date in the laboratory, we find that melting excitations have little impact on cyclization kinetics. Strong signatures of melting, which might be resolved within typical experimental scatter, emerge only for shorter chains.
DNA 弯曲的蠕虫链模型能够准确地再现长链（千碱基）的单分子力-延伸曲线。然而，这些大尺度的弯曲统计数据并不能为 1-10 碱基对（bp）尺度的弹性建立一个独特的微观模型，而在生物背景下，这一点尤其有趣。在这里，我们研究了一类微观模型，这些模型允许破坏碱基配对（即“融化”或“扭曲”，通常称为“激发”），从而提高局部灵活性。我们首先分析了在蠕虫链中整合空间自由度对激发自由能的影响。基于这一分析，我们提出了这些模型的一种表述方式，确保了与长链中已确立的熔化热力学的一致性。我们使用一种新的方法，从增强采样蒙特卡罗模拟中计算短链的环化统计，我们计算了可熔化蠕虫链在广泛的链长范围内的 J 因子，包括尚未在实验中探索过的非常短的分子（30bp）。对于长于约 120bp 的链，包括迄今为止实验室中研究的大多数分子，我们发现熔化激发对环化动力学几乎没有影响。只有对于较短的链，才会出现可能在典型实验散射范围内分辨出的强烈熔化特征。
