Battistini, FedericaHospital, AdamBuitrago Ospina, Diana CamilaGallego Perez, DiegoDans, Pablo D.Gelpí Buchaca, Josep LluísOrozco López, Modesto2020-03-262020-07-172019-07-170022-2836https://hdl.handle.net/2445/153994The 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.15 p.application/pdfengcc-by-nc-nd (c) Elsevier Ltd, 2019http://creativecommons.org/licenses/by-nc-nd/3.0/esGenètica molecularProteïnesMolecular geneticsProteinsinfo:eu-repo/semantics/article6913042020-03-26info:eu-repo/semantics/openAccess