Joint IRB BSC Research Program in Computational Biology, Institute for Research in Biomedicine, Baldiri Reixach 10, Barcelona 08028, Spain.
J Am Chem Soc. 2012 Apr 18;134(15):6596-606. doi: 10.1021/ja209786t. Epub 2012 Apr 6.
Extensive (more than 90 microseconds) molecular dynamics simulations complemented with ion-mobility mass spectrometry experiments have been used to characterize the conformational ensemble of DNA triplexes in the gas phase. Our results suggest that the ensemble of DNA triplex structures in the gas phase is well-defined over the experimental time scale, with the three strands tightly bound, and for the most abundant charge states it samples conformations only slightly more compact than the solution structure. The degree of structural alteration is however very significant, mimicking that found in duplex and much larger than that suggested for G-quadruplexes. Our data strongly supports that the gas phase triplex maintains an excellent memory of the solution structure, well-preserved helicity, and a significant number of native contacts. Once again, a linear, flexible, and charged polymer as DNA surprises us for its ability to retain three-dimensional structure in the absence of solvent. Results argue against the generally assumed roles of the different physical interactions (solvent screening of phosphate repulsion, hydrophobic effect, and solvation of accessible polar groups) in modulating the stability of DNA structures.
通过与离子迁移质谱实验相结合的广泛（超过 90 微秒）分子动力学模拟，已经对气相中 DNA 三螺旋的构象整体进行了特征描述。我们的研究结果表明，在实验时间尺度内，气相中 DNA 三螺旋结构的整体是明确的，三条链紧密结合，对于最丰富的电荷态，它仅略微比溶液结构更紧凑地采样构象。然而，结构改变的程度非常显著，模拟了在双链中发现的结构，并远大于对 G-四链体的结构改变。我们的数据强烈表明，气相三螺旋保留了对溶液结构的出色记忆，保持了良好的螺旋性和大量的天然接触。再一次，线性、灵活和带电聚合物如 DNA 令人惊讶的是，它在没有溶剂的情况下能够保留三维结构。研究结果反驳了一般假设的不同物理相互作用（磷酸根排斥的溶剂屏蔽、疏水性效应和可及极性基团的溶剂化）在调节 DNA 结构稳定性中的作用。
