Modeling Spatial Correlation of DNA Deformation: DNA Allostery in Protein Binding
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Author(s)
Xu, Xinliang
Ge, Hao
Gu, Chan
Gao, Yi Qin
Wang, Siyuan S.
Thio, Beng Joo Reginald
Hynes, James T.
Xie, X. Sunney
Cao, Jianshu
Date Issued
October 2013
Journal
Journal of Physical Chemistry B
Publisher
American Chemical Society
Citation
Xu, Xinliang, Hao Ge, Chan Gu, Yi Qin Gao, Siyuan S. Wang, Beng Joo Reginald Thio, James T. Hynes, X. Sunney Xie, and Jianshu Cao. “Modeling Spatial Correlation of DNA Deformation: DNA Allostery in Protein Binding.” The Journal of Physical Chemistry B 117, no. 42 (October 24, 2013): 13378–13387.
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Author's final manuscript
Abstract
We report a study of DNA deformations using a coarse-grained mechanical model and quantitatively interpret the allosteric effects in protein–DNA binding affinity. A recent single-molecule study (Kim et al. Science 2013, 339, 816) showed that when a DNA molecule is deformed by specific binding of a protein, the binding affinity of a second protein separated from the first protein is altered. Experimental observations together with molecular dynamics simulations suggested that the origin of the DNA allostery is related to the observed deformation of DNA’s structure, in particular, the major groove width. To unveil and quantify the underlying mechanism for the observed major groove deformation behavior related to the DNA allostery, here we provide a simple but effective analytical model where DNA deformations upon protein binding are analyzed and spatial correlations of local deformations along the DNA are examined. The deformation of the DNA base orientations, which directly affect the major groove width, is found in both an analytical derivation and coarse-grained Monte Carlo simulations. This deformation oscillates with a period of 10 base pairs with an amplitude decaying exponentially from the binding site with a decay length lD ≈10 base pairs as a result of the balance between two competing terms in DNA base-stacking energy. This length scale is in agreement with that reported from the single-molecule experiment. Our model can be reduced to the worm-like chain form at length scales larger than lP but is able to explain DNA’s mechanical properties on shorter length scales, in particular, the DNA allostery of protein–DNA interactions.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/jp4047243
