Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

86-POS

Board 6

Twisting DNA Anna Reymer 1,2 , Krystyna Zakrzewska 2 , Richard Lavery 2 . 1 University of Gothenburg, Gothenburg, Sweden, 2 Université Lyon 1 / CNRS UMR 5086, IBCP, Lyon, France. Ability of DNA to dynamically change its superhelical state is central to many biological functions, including regulation of gene expression, repair, and packaging in the cell. To address conformational mechanics of DNA during supercoiling transitions we designed a new structural constraint, implemented in PLUMED free energy library environment package, which can be used in complement with standard all-atom molecular dynamics software. The constraint controls the value of total twist between any two base-pairs in a DNA molecule, while it does not restrict any other DNA helical parameter. The constraint can be applied to DNA molecules of any length and curvature, alone or in complex with other molecules. This allows for the first time to study DNA in conditions resembling its in vivo state, where DNA’s topology is substantially restricted. As a proof of concept, we applied the restraint to four different linear DNA molecules, changing their superhelical density from -0.15 to +0.15, which corresponds to under- or overwinding by 5 degrees per base pair step. DNA’s response to the torsional stress is discontinuous − certain dinucleotide steps are more susceptible to modifying their twist through coupled changes in the phosphodiester backbone. This allows the remaining base pair steps to stay close to a canonical B-form conformation despite the overall torsional restraint. These findings constitute a new aspect of how DNA sequence can contribute to biological regulation mechanisms.

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