Probing helical transitions in a DNA duplex
Probing helical transitions in a DNA duplex
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DOI：
10.1039/c6cp06309h
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发表时间：
2017-01-07
影响因子：
3.3
通讯作者：
Wales, David J.
中科院分区：
文献类型：
--
作者：
Chakraborty, Debayan;Wales, David J.
从B-DNA到Z-DNA的复杂构象变化需要反转螺旋手性。在这个转换过程中，多个自由度错综复杂地耦合在一起，制定一个适当的反应坐标来捕捉潜在的复杂性是有问题的。在这篇文章中，我们采用了另一种方法，基于势能景观的观点，来构建一个动力学转换网络。对B -> - Z跃迁的微观洞察是根据几何上定义的离散路径提供的，该路径由局部极小值和连接它们的跃迁状态组成。我们发现手性反转可以通过两种相互竞争的机制发生，要么涉及拉伸的中间体，要么涉及B-Z结，这与之前的预测一致。自由能景观的组织进一步表明，在生理条件下，这一过程可能是缓慢的。我们的结果代表了解码B -> Z跃迁更有趣的特征的关键一步，例如离子强度和负超线圈在重塑景观中的作用。
The complex conformational change from B-DNA to Z-DNA requires inversion of helix-handedness. Multiple degrees of freedom are intricately coupled during this transition, and formulating an appropriate reaction coordinate that captures the underlying complexity would be problematic. In this contribution, we adopt an alternative approach, based on the potential energy landscape perspective, to construct a kinetic transition network. Microscopic insight into the B -> Z transition is provided in terms of geometrically defined discrete paths consisting of local minima and the transition states that connect them. We find that the inversion of handedness can occur via two competing mechanisms, either involving stretched intermediates, or a B-Z junction, in agreement with previous predictions. The organisation of the free energy landscape further suggests that this process is likely to be slow under physiological conditions. Our results represent a key step towards decoding the more intriguing features of the B -> Z transition, such as the role of ionic strength and negative supercoiling in reshaping the landscape.