Modeling Spatial Correlation of DNA Deformation: DNA Allostery in Protein Binding

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• 作者：Xinliang Xu ; Hao Ge ; Chan Gu ; Yi Qin Gao ; Siyuan S. Wang ; Beng Joo Reginald Thio ; James T. Hynes ; X. Sunney Xie ; Jianshu Cao
• 刊名：Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：October 24, 2013
• 年：2013
• 卷：117
• 期：42
• 页码：13378-13387
• 全文大小：413K
• 年卷期：v.117,no.42(October 24, 2013)
• ISSN：1520-5207

文摘

We report a study of DNA deformations using a coarse-grained mechanical model and quantitatively interpret the allosteric effects in protein鈥揇NA binding affinity. A recent single-molecule study (Kim et al. <i>Sciencei> 2013, <i>339i>, 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鈥檚 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 <i>li>_D 鈮?0 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 <i>li>_P but is able to explain DNA鈥檚 mechanical properties on shorter length scales, in particular, the DNA allostery of protein鈥揇NA interactions.