Twisting DNA by Salt

Abstract

DNA structure and properties sensitively depend on its environment, in particular on the ion atmosphere. One of the most fundamental properties of DNA is its helicity and here we investigate how it changes with concentration and identity of the surrounding ions. To resolve how metal cations influence the helical twist, we have combined magnetic tweezer experiments and extensive all-atom molecular dynamics simulations. Two interconnected trends are observed for monovalent alkali and divalent alkaline earth cations. First, DNA twist increases with increasing ion concentration. Secondly, for a given salt concentration, DNA twist strongly depends on cation identity. Metal cations with high charge density (such as Li+ or Ca2+) are most efficient at inducing DNA twist and lead to overwinding. By contrast, metals with intermediate charge density (such as Na+ or Ba2+) reduce the twist and underwind the helix compared to higher density ions. Our molecular dynamics simulations reveal that preferential binding of the metals to the DNA backbone and the nucleobases has opposing effects on DNA twist and provide a microscopic explanation of the observed ion specificity. The comprehensive view gained from our combined approach provides a foundation to understand and predict metal-induced structural changes in nature or in DNA nanotechnology.

Optimized Magnesium Force Field Parameters for Biomolecular Simulations with Accurate Solvation, Ion-Binding, and Water-Exchange Properties in SPC/E, TIP3P-fb, TIP4P/2005, TIP4P-Ew, and TIP4P-D

“…83 In addition, including experimental binding affinities toward specific ion binding sites on biomolecules has turned out to be essential to capture the structure of specifically bound ions 26 as well as to reproduce the structural properties of large nucleic acids. 42 Two parameter sets are presented for each water model: The first sets, microMg, yield water exchange on the microsecond time scale in agreement with experimental results. 73,74 For the second sets, nanoMg, the parameters were chosen to yield the highest exchange rate possible while still reproducing all other thermodynamic and structural properties.…”

Using capillary electrophoresis to characterize the hydrodynamic and electrostatic properties of DNA in solutions containing various monovalent cations

“…Hence, even at high ionic strengths, the phased A‐tracts in ds98‐4in localized more monovalent cations than the out‐of‐phase A‐tracts in ds98‐4out, decreasing the effective net charge of ds98‐4in. The results suggest that subtle differences in the structure of DNAs with phased A‐tracts, possibly ionic strength‐induced twisting of the helix backbone [86], could lead to cation exchange between adjacent A‐tracts without cation dissociation, allowing preferential cation localization to occur in ds98‐4in but not in ds98‐4out. Ligand exchange between equivalent binding sites in A‐tract DNAs, without ligand dissociation, has been observed for other minor‐groove binding molecules [87].…”

Magnesium Force Fields for OPC Water with Accurate Solvation, Ion-Binding, and Water-Exchange Properties: Successful Transfer from SPC/E

“…Moreover, the SPC/E-optimized parameters closely reproduce the binding affinity of Mg 2+ toward the phosphate oxygen of RNA. Matching the binding affinity of metal cations to specific ion binding sites is particularly important since it improves the agreement between experiments and simulations for the structure and properties of larger nucleic acid systems 68 .…”