Modeling Spatial Correlation of DNA Deformation: DNAAllostery in Protein Binding.

We report a study of DNA deformationsusing a coarse-grained mechanicalmodel and quantitatively interpret the allosteric effects in protein–DNAbinding affinity. A recent single-molecule study (Kim et al. Science2013, 339, 816) showedthat when a DNA molecule is deformed by specific binding of a protein,the binding affinity of a second protein separated from the firstprotein is altered. Experimental observations together with moleculardynamics simulations suggested that the origin of the DNA allosteryis related to the observed deformation of DNA’s structure,in particular, the major groove width. To unveil and quantify theunderlying mechanism for the observed major groove deformation behaviorrelated to the DNA allostery, here we provide a simple but effectiveanalytical model where DNA deformations upon protein binding are analyzedand spatial correlations of local deformations along the DNA are examined.The deformation of the DNA base orientations, which directly affectthe major groove width, is found in both an analytical derivationand coarse-grained Monte Carlo simulations. This deformation oscillateswith a period of 10 base pairs with an amplitude decaying exponentiallyfrom the binding site with a decay length lD≈10 base pairs as a result of the balance between two competingterms in DNA base-stacking energy. This length scale is in agreementwith that reported from the single-molecule experiment. Our modelcan be reduced to the worm-like chain form at length scales largerthan lPbut is able to explain DNA’smechanical properties on shorter length scales, in particular, theDNA allostery of protein–DNA interactions. [ABSTRACT FROM AUTHOR]