Li Hui, Cao En-hua, Gisler Thomas
Universität Konstanz, Fachbereich Physik, Konstanz, Germany.
Biochem Biophys Res Commun. 2009 Jan 30;379(1):70-5. doi: 10.1016/j.bbrc.2008.12.006. Epub 2008 Dec 13.
We study the unfolding of a parallel G-quadruplex from human telomeric DNA by mechanical stretching using steered molecular dynamics (MD) simulation. We find that the force curves and unfolding processes strongly depend on the pulling sites. With pulling sites located on the sugar-phosphate backbone, the force-extension curve shows a single peak and the unfolding proceeds sequentially. Pulling sites located on the terminal nucleobases lead to a force-extension curve with two peaks and the unfolding is more cooperative. Simulations of the refolding of partially unfolded quadruplexes show very different behavior for the two different pulling modalities. In particular, starting from an unfolded state prepared by nucleobase pulling leads to a long-lived intermediate state whose existence is also corroborated by the free energy profile computed with the Jarzynski equation. Based on this observation, we propose a novel folding pathway for parallel G-quadruplexes with the human telomere sequence.
我们通过使用引导分子动力学（MD）模拟的机械拉伸来研究来自人类端粒DNA的平行G-四链体的解折叠。我们发现力曲线和解折叠过程强烈依赖于拉动位点。当拉动位点位于糖-磷酸主链上时，力-伸长曲线显示出一个单峰，并且解折叠是顺序进行的。位于末端核碱基上的拉动位点导致力-伸长曲线有两个峰，并且解折叠更协同。对部分解折叠的四链体的重新折叠模拟显示了两种不同拉动方式的非常不同的行为。特别是，从通过核碱基拉动制备的解折叠状态开始会导致一个长寿命的中间状态，其存在也通过用雅津斯基方程计算的自由能分布得到证实。基于这一观察结果，我们提出了一种具有人类端粒序列的平行G-四链体的新型折叠途径。
