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Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
123
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.