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Accurate modeling of DNA conformational flexibility by a multivariate Ising model.
Liebl, Korbinian; Zacharias, Martin.
Afiliação
  • Liebl K; Physics Department T38, Technical University of Munich, 85748 Garching, Germany.
  • Zacharias M; Physics Department T38, Technical University of Munich, 85748 Garching, Germany martin.zacharias@mytum.de.
Proc Natl Acad Sci U S A ; 118(15)2021 04 13.
Article em En | MEDLINE | ID: mdl-33876759
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Modelos Teóricos / Conformação de Ácido Nucleico Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Modelos Teóricos / Conformação de Ácido Nucleico Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article