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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/153994
How B-DNA dynamics decipher sequence-selective protein recognition
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The rules governing sequence-specific DNA-protein recognition are under a long-standing debate regarding the prevalence of base versus shape readout mechanisms to explain sequence specificity and of the conformational selection versus induced fit binding paradigms to explain binding-related conformational changes in DNA. Using a combination of atomistic simulations on a subset of representative sequences and mesoscopic simulations at the protein-DNA interactome level, we demonstrate the prevalence of the shape readout model in determining sequence-specificity and of the conformational selection paradigm in defining the general mechanism for binding-related conformational changes in DNA. Our results suggest that the DNA uses a double mechanism to adapt its structure to the protein: it moves along the easiest deformation modes to approach the bioactive conformation, while final adjustments require localized rearrangements at the base-pair step and backbone level. Our study highlights the large impact of B-DNA dynamics in modulating DNA-protein binding.
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BATTISTINI, Federica, et al. How B-DNA dynamics decipher sequence-selective protein recognition. Journal of Molecular Biology. 2019. Vol. 431, num. 3845-3859. ISSN 0022-2836. [consulted: 10 of October of 2026]. Available at: https://hdl.handle.net/2445/153994