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DNA melting and energetics of the double helix
Physics of Life Reviews ( IF 11.7 ) Pub Date : 2017-11-14 , DOI: 10.1016/j.plrev.2017.11.012
Alexander Vologodskii , Maxim D. Frank-Kamenetskii

Studying melting and energetics of the DNA double helix has been one of the major topics of molecular biophysics over the past six decades. The main objective of this article is to overview the current state of the field and to emphasize that there are still serious gaps in our understanding of the issue. We start with a concise description of the commonly accepted theoretical model of the DNA melting. We then concentrate on studies devoted to the comparison with experiment of theoretically predicted melting profiles of DNAs with known sequences. For long DNA molecules, such comparison is significant from the basic-science viewpoint while an accurate theoretical description of melting of short duplexes is necessary for various very important applications in biotechnology. Several sets of DNA melting parameters, proposed within the framework of the nearest neighbor model, are compared and analyzed. The analysis leads to a conclusion that in case of long DNA molecules the consensus set of nearest neighbor parameters describes well the experimental melting profiles. Unexpectedly, for short DNA duplexes the same set of parameters hardly yields any improvement as compared to the simplest model, which completely ignores the effect of heterogeneous stacking. Possible causes of this striking observation are discussed. We then overview the issue of separation of base-pairing and base-stacking contributions into the double helix stability. The recent experimental attempts to solve the problem are extensively analyzed. It is concluded that the double helix is essentially stabilized by stacking interaction between adjacent base pairs. Base pairing between complementary pairs does not appreciably contribute into the duplex stability. In the final section of the article, kinetic aspects of the DNA melting phenomenon are discussed. The main emphasis is made on the hysteresis effects often observed in melting of long DNA molecules. It is argued that the phenomenon can be well described via an accurate theoretical treatment of the random-walk model of melting kinetics of an isolated helical segment in DNA.



中文翻译:

双螺旋的DNA熔解和能量学

在过去的六十年中,研究DNA双螺旋的解链和能量学一直是分子生物物理学的主要主题之一。本文的主要目的是概述该领域的当前状况,并强调我们对这一问题的理解仍然存在严重差距。我们从对DNA融合的普遍接受的理论模型的简要描述开始。然后,我们专注于致力于与具有已知序列的DNA的理论预测熔解谱进行实验比较的研究。对于长DNA分子,从基础科学的角度来看,这样的比较是有意义的,而短双链体的熔化的准确理论描述对于生物技术中各种非常重要的应用是必要的。几套DNA熔解参数,在最近邻居模型的框架内提出的建议,进行了比较和分析。分析得出的结论是,在长DNA分子的情况下,最接近的邻居参数的共有集很好地描述了实验熔解曲线。出乎意料的是,对于短DNA双链体,与最简单的模型相比,相同的参数集几乎没有任何改善,后者完全忽略了异质堆叠的影响。讨论了这种惊人观察的可能原因。然后,我们概述了将碱基配对和碱基堆积贡献分离为双螺旋稳定性的问题。解决该问题的最新实验尝试已得到广泛分析。结论是,通过相邻碱基对之间的堆叠相互作用基本稳定了双螺旋。互补对之间的碱基配对不会明显影响双链体的稳定性。在文章的最后部分,讨论了DNA融合现象的动力学方面。主要重点是在长DNA分子融化中经常观察到的磁滞效应。据认为,该现象可以通过对孤立的DNA螺旋段的解链动力学的随机游走模型进行精确的理论处理来很好地描述。

更新日期:2017-11-14
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