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 language | English |
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Article number | e2021263118 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 118 |
Issue number | 15 |
DOIs | |
State | Published - 13 Apr 2021 |
Externally published | Yes |
Keywords
- DNA deformability
- Indirect readout
- Nearest-neighbor model
- Protein-DNA binding