Twisting DNA by salt

Abstract

The structure and properties of DNA depend on the environment, in particular the ion atmosphere. Here, we investigate how DNA twist -one of the central properties of DNA- changes with concentration and identity of the surrounding ions. To resolve how cations influence the twist, we combine single-molecule 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 monotonously with increasing concentration for all ions investigated. Second, for a given salt concentration, DNA twist strongly depends on cation identity. At 100 mM concentration, DNA twist increases as Na+ < K+ < Rb+ < Ba2+ < Li+ ≈ Cs+ < Sr2+ < Mg2+ < Ca2+. Our molecular dynamics simulations reveal that preferential binding of the cations to the DNA backbone or the nucleobases has opposing effects on DNA twist and provides the microscopic explanation of the observed ion specificity. However, the simulations also reveal shortcomings of existing force field parameters for Cs+ and Sr2+. The comprehensive view gained from our combined approach provides a foundation for understanding and predicting cation-induced structural changes both in nature and 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

“…Here, an alternative and promising approach for future work is the simultaneous optimization of anion and cations parameters, which eliminates the necessity to select a reference ion . 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 as well as to reproduce the structural properties of large nucleic acids …”

“…In principle, it is possible to combine more advanced water models and ion parameters with the force fields for biomolecules. In some cases, such a combination can leverage the strengths of the respective parameters and improve the agreement between simulated and experimental structures. ,− However, the combination of force field parameters does not guarantee that the physical properties, which were targeted in the first place, are reproduced. For metal cations, previous studies indicate limited transferability and different water models can have significant effects on the solvation free energy, the exchange kinetics, and even the reaction mechanism. − It is therefore crucial to assess the transferability of Mg 2+ parameters to different water models and optimize the force field parameters if necessary in order to ensure physically meaningful results.…”

Magnesium force fields for OPC water with accurate solvation, ion-binding, and water-exchange properties: Successful transfer from SPC/E

“…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. 64 In summary, the SPC/E-optimized parameter sets microMg and nanoMg provide an efficient and highly accurate model for the simulation of Mg 2+ in OPC water.…”

Ab initio predictions for 3D structure and stability of single- and double-stranded DNAs in ion solutions

“…Although several experimental methods such as cryo-electron microscopy, X-ray crystallography, NMR spectroscopy, and other single-molecule techniques (e.g., optical/magnetic tweezers and atomic force microscopy) can be used to determine three-dimensional (3D) structures or elastic properties of DNAs (10)(11)(12)(13)(14)(15), there are still full of challenges (e.g., time-consuming and expensive) to experimentally provide insight into DNA folding/hybridization. Thus, the field of computer simulation is rapidly evolving to provide finer details on key features of DNA biophysics compared to experimental approaches (16)(17)(18)(19).…”

“…In addition, due to the polyanionic nature of DNAs, metal ions (e.g., Na + and Mg 2+ ) in solutions can play an essential role in DNA folding and dynamics (12)(13)(14)(61)(62)(63)(64). Although several of the existing models such as 3SPN, oxDNA, TIS, and NARES-2P have taken the electrostatic interactions into account using the Debye-Huckel approximation or mean-field multipole-multipole potentials and reproduced some monovalent salt-dependent structural properties (e.g., persistence length, torsional stiffness or melting temperatures) of DNAs (45,48,50,57), quantitatively predicting the 3D structure and thermodynamic stability for DNA including both ssDNA and dsDNA in ion solutions (especially divalent ions) from the sequence is still an unresolved problem.…”