How B-DNA Dynamics Decipher Sequence-Selective Protein Recognition

TitleHow B-DNA Dynamics Decipher Sequence-Selective Protein Recognition
Publication TypeJournal Article
Year of Publication2019
AuthorsBattistini, Federica, Hospital Adam, Buitrago Diana, Gallego Diego, Dans Pablo D., Gelpí Josep Lluis, and Orozco Modesto
JournalJournal of Molecular Biology
Date Published07/2019
ISBN Number0022-2836
KeywordsDNA-protein recognition, molecular dynamics, PDB data mining, Principal Component Analysis, Structural analysis
Abstract

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 localised rearrangements at the base pair step and backbone level. Our study highlights the large impact of B-DNA dynamics in modulating DNA-protein binding.

URLhttp://www.sciencedirect.com/science/article/pii/S0022283619304516
Short TitleJournal of Molecular Biology
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