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- W1988397229 abstract "Several proteins are known to produce significant changes in DNA shape by locally deforming the double helix or by mediating the formation a loop. For example, the binding of the bacterial proteins HU or Hbb produces large bends in DNA and the tetrameric Lac repressor protein induces the formation of a loop between two distant DNA operators. In order to understand how such proteins sculpt DNA, we have developed a novel optimization method for DNA at the base-pair level. Our method accounts for the sequence-dependent elasticity of DNA and can be applied to a DNA fragment in which the first and last base pairs are spatially constrained. Moreover, our approach makes it possible to constrain intervening parts of the DNA in order to model the presence of bound proteins. We can therefore compute the energy landscape for a wide variety of protein-DNA systems. For example, we studied the effect of the presence of multiple HU or Hbb proteins on DNA minicircles and identified the most likely configurations for given DNA chain lengths and numbers of bound proteins. We also investigated how the presence of HU can enhance or diminish the apparent flexibility of DNA. In addition, we performed a detailed analysis of the energy landscape for loops induced by the Lac repressor. We focused on the binding of the Lac repressor protein on DNA minicircles and studied the competition between large and small loops on supercoiled molecules. We also found that changes in the repressor structure can lead to different loop topologies. Our method makes it possible to conduct thorough analyses of the geometry and mechanics of protein-DNA systems by computing the associated energy landscape and paves the way for the study of other biologically relevant system such as the SV40 minichromosome." @default.
- W1988397229 created "2016-06-24" @default.
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- W1988397229 date "2014-01-01" @default.
- W1988397229 modified "2023-09-30" @default.
- W1988397229 title "Understanding How Proteins Shape DNA Using Energy Minimization" @default.
- W1988397229 doi "https://doi.org/10.1016/j.bpj.2013.11.466" @default.
- W1988397229 hasPublicationYear "2014" @default.
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