Elasticity as the Basis of Allostery in DNA

Allosteric
interactions in DNA are crucial for various biological
processes. These interactions are quantified by measuring the change
in free energy as a function of the distance between the binding sites
for two ligands. Here, we show that trends in the interaction energy
of ligands binding to DNA can be explained within an elastic birod
model, which accounts for the deformation of each strand as well as
the change in stacking energy due to perturbations in position and
orientation of the bases caused by the binding of ligands. The strain
fields produced by the ligands decay with distance from the binding
site. The interaction energy of two ligands decays exponentially with
the distance between them and oscillates with the periodicity of the
double helix in quantitative agreement with experimental measurements.
The trend in the computed interaction energy is similar to that in
the perturbation of groove width produced by the binding of a single
ligand, which is consistent with molecular simulations. Our analysis
provides a new framework to understand allosteric interactions in
DNA and can be extended to other rod-like macromolecules whose elasticity
plays a role in biological functions.