Probing helical transitions in a DNA duplex
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Publication Date
2017-01-07Journal Title
Physical Chemistry Chemical Physics
ISSN
1463-9076
Publisher
Royal Society of Chemistry
Volume
19
Issue
1
Pages
878-892
Language
English
Type
Article
This Version
AM
Metadata
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Chakraborty, D., & Wales, D. (2017). Probing helical transitions in a DNA duplex. Physical Chemistry Chemical Physics, 19 (1), 878-892. https://doi.org/10.1039/c6cp06309h
Abstract
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.
Sponsorship
The work was financially supported by the ERC. D. C. gratefully acknowledges the Cambridge Commonwealth, European and International Trust for a PhD fellowship.
Identifiers
External DOI: https://doi.org/10.1039/c6cp06309h
This record's URL: https://www.repository.cam.ac.uk/handle/1810/262785
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