Accurate modeling of DNA conformational flexibility by a multivariate Ising model

Korbinian Liebl, Martin Zacharias

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The sequence-dependent structure and deformability of DNA play a major role for binding of proteins and regulation of gene expression. So far, most efforts to model DNA flexibility are based on unimodal harmonic stiffness models at base-pair resolution. However, multimodal behavior due to distinct conformational substates also contributes significantly to the conformational flexibility of DNA. Moreover, these local substates are correlated to their nearest-neighbor substates. A description for DNA elasticity which includes both multimodality and nearest-neighbor coupling has remained a challenge, which we solve by combining our multivariate harmonic approximation with an Ising model for the substates. In a series of applications to DNA fluctuations and protein-DNA complexes, we demonstrate substantial improvements over the unimodal stiffness model. Furthermore, our multivariate Ising model reveals a mechanical destabilization for adenine (A)-tracts to undergo nucleosome formation. Our approach offers a wide range of applications to determine sequence-dependent deformation energies of DNA and to investigate indirect readout contributions to protein-DNA recognition.

Original languageEnglish
Article numbere2021263118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number15
DOIs
StatePublished - 13 Apr 2021
Externally publishedYes

Keywords

  • DNA deformability
  • Indirect readout
  • Nearest-neighbor model
  • Protein-DNA binding

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