Transitions of Double-Stranded DNA Between the A- and B-Forms
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- 作者：James T. Waters ; Xiang-Jun Lu ; Rodrigo Galindo-Murillo ; James C. Gumbart ; Harold D. Kim ; Thomas E. Cheatham III ; Stephen C. Harvey
- 刊名：Journal of Physical Chemistry B
- 出版年：2016
- 出版时间：August 25, 2016
- 年：2016
- 卷：120
- 期：33
- 页码：8449-8456
- 全文大小：639K
- 年卷期：0
- ISSN：1520-5207
文摘
The structure of double-stranded DNA (dsDNA) is sensitive to solvent conditions. In solution, B-DNA is the favored conformation under physiological conditions, while A-DNA is the form found under low water activity. The A-form is induced locally in some protein–DNA complexes, and repeated transitions between the B- and A-forms have been proposed to generate the forces used to drive dsDNA into viral capsids during genome packaging. Here, we report analyses on previous molecular dynamics (MD) simulations on B-DNA, along with new MD simulations on the transition from A-DNA to B-DNA in solution. We introduce the A-B Index (ABI), a new metric along the A-B continuum, to quantify our results. When A-DNA is placed in an equilibrated solution at physiological ionic strength, there is no energy barrier to the transition to the B-form, which begins within about 1 ns. The transition is essentially complete within 5 ns, although occasionally a stretch of a few base pairs will remain A-like for up to ∼10 ns. A comparison of four sequences with a range of predicted A-phobicities shows that more A-phobic sequences make the transition more rapidly than less A-phobic sequences. Simulations on dsDNA with a region of roughly one turn locked in the A-form allow us to characterize the A/B junction, which has an average bend angle of 20–30°. Fluctuations in this angle occur with characteristic times of about 10 ns.