Generalized theory of site-specific DNA-protein interactions.
We develop a generalized theory of the site-specific DNA-protein interactions, which includes both the static as well as the dynamical factors influencing the one-dimensional diffusion of the nonspecifically bound protein molecule which is in the process of searching for the specific site on the DNA lattice. We argue that the chemically driven condensation of the DNA molecule introduces a static distribution in the one-dimensional phenomenological diffusion coefficient associated with the protein molecule and the conformational dynamics of the DNA introduces temporal fluctuations in the one-dimensional diffusion coefficient over the static distribution. We further derive the generalized inequality conditions and the scaling laws which are required to enhance the three-dimensional diffusion controlled site-specific association rate to an arbitrary order. Our model predicts that when the degree of condensation of the DNA molecule under consideration is very high, then the probability distribution associated with the stationary state one-dimensional diffusion coefficient variable as well as the stationary state one-dimensional diffusion length variable will be a flat one. Further analysis reveals that to achieve a site-specific association rate which is higher than that of the three-dimensional diffusion controlled rate, the one-dimensional diffusion length associated with the dynamics of the nonspecifically bound protein molecule on the DNA lattice should fall in certain critical ranges. Comparison of our theoretical results with the recent experimental observations reveals that when the DNA molecule is under a stretched condition, then the static distribution of the one-dimensional diffusion coefficient associated with the dynamics of the protein molecule on the DNA lattice is a Gaussian and therefore the fluctuations in the one-dimensional diffusion coefficient generated by the dynamical factors are confined in a harmonic type potential.
Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, 400005, India. rmurugan@gmail.com
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D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D004058:Diffusion; D008956:Models, Chemical; D008958:Models, Molecular; D009038:Motion; D011485:Protein Binding
D004268:DNA-Binding Proteins; D004247:DNA