The folding of centromeric DNA strands into intercalated structures: a physicochemical and computational study.
The folding of centromeric DNA strands into intercalated structures: a physicochemical and computational study.
复制标题
DOI：
10.1006/jmbi.1998.2334
复制
发表时间：
1999-01
影响因子：
5.6
通讯作者：
J. Gallego;E. B. Golden;D. Stanley;B. Reid
中科院分区：
文献类型：
--
作者：
J. Gallego;E. B. Golden;D. Stanley;B. Reid
我们对富含胞嘧啶的DNA链形成的插层结构的稳定性进行了物理化学和计算分析。在计算研究中，静电能量分量用泊松-玻尔兹曼模型计算，非极性能量分量用van der Waals函数和/或依赖于分子的溶剂可及表面积的项计算。计算结果与Watson-Crick双链的结果以及从UV实验得到的热力学数据进行了比较。我们发现，插层DNA主要是通过氢键、质子化和中性胞嘧啶之间非常有利的静电相互作用以及包括疏水效应和增强的范德华接触在内的非极性作用力来稳定的。胞嘧啶质子化在静电作用下促进DNA链结合成四聚体结构。堆积的C.C+对之间的静电相互作用被溶剂的反应场强烈地衰减，并受到几何因素和质子化因素的复杂相互作用的调制。稳定插层DNA的力必须抵消在中性pH下由于胞嘧啶质子化吸收质子而产生的熵惩罚，以及静电对溶剂化自由能的贡献。后一种能量分量对质子化的DNA不太有利，因为分子的负电荷被部分中和，并可能影响其他质子化的DNA和RNA结构，如含C+的三链。
We have carried out a physicochemical and computational analysis on the stability of the intercalated structures formed by cytosine-rich DNA strands. In the computational study, the electrostatic energy components have been calculated using a Poisson-Boltzmann model, and the non-polar energy components have been computed with a van der Waals function and/or a term dependent on the solvent-accessible surface area of the molecules. The results have been compared with those obtained for Watson-Crick duplexes and with thermodynamic data derived from UV experiments. We have found that intercalated DNA is mainly stabilized by very favorable electrostatic interactions between hydrogen-bonded protonated and neutral cytosines, and by non-polar forces including the hydrophobic effect and enhanced van der Waals contacts. Cytosine protonation electrostatically promotes the association of DNA strands into a tetrameric structure. The electrostatic interactions between stacked C.C+ pairs are strongly attenuated by the reaction field of the solvent, and are modulated by a complex interplay of geometric and protonation factors. The forces stabilizing intercalated DNA must offset an entropic penalty due to the uptake of protons for cytosine protonation, at neutral pH, and also the electrostatic contribution to the solvation free energy. The latter energy component is less favorable for protonated DNA due to the partial neutralization of the negative charge of the molecule, and probably affects other protonated DNA and RNA structures such as C+-containing triplexes.