Department of Chemistry , University of Washington , Box 351700, Seattle , Washington 98195 , United States.
J Phys Chem B. 2019 Aug 29;123(34):7343-7353. doi: 10.1021/acs.jpcb.9b05139. Epub 2019 Aug 15.
Previous experimental studies of the effects of changes in sequence on the elastic constants and other properties of DNAs are analyzed using the recently parametrized two-state cooperative transition model. With appropriate assumptions regarding the relative preference of particular subsequences for the and states, the model gives an approximately quantitative account of the surprisingly large observed effects of replacing 25 bp of natural sequence near the middle of an ∼1100 bp DNA by 16 bp of alternating (CG) sequence on the fraction of base-pairs in the -state and on the torsion elastic constant. This demonstrates the effect of the strong cooperativity of the transition to significantly influence the state of the DNA over surprisingly large domains of the flanking DNA. With appropriate assumptions regarding the disposition of nonrelaxing (permanent) and slowly relaxing bends between the and states, the two-state model resolves the discrepancy between experimental estimates of the magnitude of the nonrelaxing bends obtained from studies of synthetic straight and natural DNA sequences by cryo-electron microscopy on the one hand and by -factors inferred from the kinetics of ligase cyclization of small ∼200 bp circular DNAs on the other. Approximately quantitative agreement with the experiments is again obtained.
使用最近参数化的两态协同跃迁模型，分析了先前关于序列变化对 DNA 弹性常数和其他性质影响的实验研究。通过对特定亚序列相对于 和 状态的相对偏好的适当假设，该模型可以近似定量地解释在天然序列约 1100bp 中段附近用 16bp 的交替 (CG) 序列替换 25bp 所观察到的惊人大的效应，这对碱基对在 -状态的分数 和扭转弹性常数 有影响。这表明跃迁的强协同作用显著影响了侧翼 DNA中非常大的 DNA 区域的状态。通过对 和 状态之间非松弛（永久）和缓慢松弛弯曲的适当假设，两态模型解决了通过低温电子显微镜研究合成直链和天然 DNA 序列以及通过小的 ~200bp 圆形 DNA 的连接酶环化动力学推断的非松弛弯曲的大小的实验估计之间的差异。与实验再次取得了近似定量的一致。
