Role of Specific Cations
and Water Entropy on the
Stability of Branched DNA Motif Structures
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Abstract
DNA three-way junctions (TWJs) are important intermediates
in various
cellular processes and are the simplest of a family of branched nucleic
acids being considered as scaffolds for biomolecular nanotechnology.
Branched nucleic acids are stabilized by divalent cations such as
Mg<sup>2+</sup>, presumably due to condensation and neutralization
of the negatively charged DNA backbone. However, electrostatic screening
effects point to more complex solvation dynamics and a large role
of interfacial waters in thermodynamic stability. Here, we report
extensive computer simulations in explicit water and salt on a model
TWJ and use free energy calculations to quantify the role of ionic
character and strength on stability. We find that enthalpic stabilization
of the first and second hydration shells by Mg<sup>2+</sup> accounts
for 1/3 and all of the free energy gain in 50% and pure MgCl<sub>2</sub> solutions, respectively. The more distorted DNA molecule is actually
destabilized in pure MgCl<sub>2</sub> compared to pure NaCl. Notably,
the first shell, interfacial waters have very low translational and
rotational entropy (i.e., mobility) compared to the bulk, an entropic
loss that is overcompensated by increased enthalpy from additional
electrostatic interactions with Mg<sup>2+</sup>. In contrast, the
second hydration shell has anomalously high entropy as it is trapped
between an immobile and bulklike layer. The nonmonotonic entropic
signature and long-range perturbations of the hydration shells to
Mg<sup>2+</sup> may have implications in the molecular recognition
of these motifs. For example, we find that low salt stabilizes the
parallel configuration of the three-way junction, whereas at normal
salt we find antiparallel configurations deduced from the NMR. We
use the 2PT analysis to follow the thermodynamics of this transition
and find that the free energy barrier is dominated by entropic effects
that result from the decreased surface area of the antiparallel form
which has a smaller number of low entropy waters in the first monolayer