Prediction of hybridization and melting for double-stranded nucleic acids
Prediction of hybridization and melting for double-stranded nucleic acids
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DOI：
10.1529/biophysj.103.020743
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发表时间：
2004-07-01
影响因子：
3.4
通讯作者：
Zuker, M
中科院分区：
文献类型：
--
作者：
Dimitrov, RA;Zuker, M
本文提出了一种通用的统计力学方法来描述一对有限长度的DNA或RNA分子之间的自折叠和杂交。该模型考虑了溶液中单链和双链物种的整个集合及其在不同温度下的摩尔分数。折叠和杂交模型处理可能存在于双链体末端或螺旋末端的匹配对、错配、对称和不对称内环、凸起和单碱基堆叠。探索了单链和双链物种的所有可能的构象。在此阶段，双链体中仅考虑分子间碱基对。特别是，我们专注于作为一个重要来源的螺旋形成的焓变化的单个未折叠链的相邻核苷酸残基之间的堆叠的作用，迄今为止还没有被模拟计算。单链状态随温度的变化在较高温度下会产生较大的热效应。一个重要的后果是，预测的functionpies，这是基于最近邻的能量参数的数据库确定的分子或双链体与较低的熔解温度相比，它们被用作预测工具的寡核苷酸的熔解温度，将被低估。
This article presents a general statistical mechanical approach to describe self-folding together with the hybridization between a pair of finite length DNA or RNA molecules. The model takes into account the entire ensemble of single- and double-stranded species in solution and their mole fractions at different temperatures. The folding and hybridization models deal with matched pairs, mismatches, symmetric and asymmetric interior loops, bulges, and single- base stacking that might exist at duplex ends or at the ends of helices. All possible conformations of the single- and double-stranded species are explored. Only intermolecular basepairs are considered in duplexes at this stage. In particular we focus on the role of stacking between neighboring nucleotide residues of single unfolded strands as an important source of enthalpy change on helix formation which has not been modeled computationally thus far. Changes in the states of the single strands with temperature are shown to lead to a larger heat effect at higher temperature. An important consequence of this is that predictions of enthalpies, which are based on databases of nearest-neighbor energy parameters determined for molecules or duplexes with lower melting temperatures compared with the melting temperatures of the oligos for which they are used as a predictive tool, will be underestimated.