Faculty of Frontiers of Innovative Research in Science and Technology, Konan University, Kobe, Japan.
Biophys J. 2012 Jun 20;102(12):2808-17. doi: 10.1016/j.bpj.2012.05.019. Epub 2012 Jun 19.
The thermal stability of nucleic acid structures is perturbed under the conditions that mimic the intracellular environment, typically rich in inert components and under osmotic stress. We now describe the thermodynamic stability of DNA oligonucleotide structures in the presence of high background concentrations of neutral cosolutes. Small cosolutes destabilize the basepair structures, and the DNA structures consisting of the same nearest-neighbor composition show similar thermodynamic parameters in the presence of various types of cosolutes. The osmotic stress experiments reveal that water binding to flexible loops, unstable mismatches, and an abasic site upon DNA folding are almost negligible, whereas the binding to stable mismatch pairs is significant. The studies using the basepair-mimic nucleosides and the peptide nucleic acid suggest that the sugar-phosphate backbone and the integrity of the basepair conformation make important contributions to the binding of water molecules to the DNA bases and helical grooves. The study of the DNA hydration provides the basis for understanding and predicting nucleic acid structures in nonaqueous solvent systems.
在模拟细胞内环境的条件下,核酸结构的热稳定性会受到干扰,通常富含惰性成分并承受渗透压应激。我们现在描述在高背景浓度中性共溶剂存在下的 DNA 寡核苷酸结构的热力学稳定性。小共溶剂会破坏碱基对结构,并且由相同最近邻组成的 DNA 结构在存在各种类型的共溶剂时表现出相似的热力学参数。渗透压应激实验表明,水在 DNA 折叠时与柔性环、不稳定的错配以及无碱基位点的结合几乎可以忽略不计,而与稳定的错配碱基对的结合则非常显著。使用碱基对模拟核苷和肽核酸的研究表明,糖磷酸骨架和碱基对构象的完整性对水分子与 DNA 碱基和螺旋沟槽的结合有重要贡献。对 DNA 水合作用的研究为理解和预测非水溶剂系统中的核酸结构提供了基础。