Counting the ions surrounding nucleic acids

Jacobson, David R.; Saleh, Omar A.

doi:10.1093/nar/gkw1305

Cited by 36 publications

(52 citation statements)

References 98 publications

(137 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The DH model assumes that macro-ion charge is equally offset by cation attraction and anion exclusion, i.e., that the local ionic strength near the NA is equal to the bulk value (37). However, it is known that, for highly charged chains such as ssNAs, I is significantly elevated close to the chain compared with the bulk due to preferential attraction of cations (38). For example, locally elevated ionic strength is seen in recent experiments (39) that show roughly 0.4 more ions per nucleotide in the ssNA ion atmosphere compared with the DH prediction, a result that decreases only very slowly with bulk I .…”

Section: Discussionmentioning

confidence: 97%

Single-stranded nucleic acid elasticity arises from internal electrostatic tension

Jacobson

McIntosh

Stevens

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Understanding of the conformational ensemble of flexible polyelectrolytes, such as single-stranded nucleic acids (ssNAs), is complicated by the interplay of chain backbone entropy and saltdependent electrostatic repulsions. Molecular elasticity measurements are sensitive probes of the statistical conformation of polymers and have elucidated ssNA conformation at low force, where electrostatic repulsion leads to a strong excluded volume effect, and at high force, where details of the backbone structure become important. Here, we report measurements of ssDNA and ssRNA elasticity in the intermediate-force regime, corresponding to 5-to 100-pN forces and 50-85% extension. These data are explained by a modified wormlike chain model incorporating an internal electrostatic tension. Fits to the elastic data show that the internal tension decreases with salt, from >5 pN under 5 mM ionic strength to near zero at 1 M. This decrease is quantitatively described by an analytical model of electrostatic screening that ascribes to the polymer an effective charge density that is independent of force and salt. Our results thus connect microscopic chain physics to elasticity and structure at intermediate scales and provide a framework for understanding flexible polyelectrolyte elasticity across a broad range of relative extensions.single-stranded nucleic acids | flexible polyelectrolytes | force spectroscopy | electrostatics S ingle-stranded nucleic acids (ssNAs) occur in many biological processes, such as RNA folding (1, 2) and DNA replication (3-5), generally in disordered conformations that fluctuate between various structures. These fluctuations create a significant entropic elasticity; thus, direct measurements of molecular elasticity (extension, X , as a function of applied force, fapp) constitute a powerful tool for studying the ssNA structural ensemble (6). In particular, measurements at a particular fapp are sensitive to the conformation within the corresponding tensile length, kB T /fapp (to within a scaling factor), where kB T is the thermal energy (7).ssNA structure-and that of flexible polyelectrolytes more generally-is complicated by the strong negative charge of the molecule. Multiple electrostatic and structural length scales share a similar magnitude (roughly 1 nm), disallowing models that consider only electrostatics or only backbone structure. In an uncharged flexible chain, the key structural scale is the persistence length, lp, defining the distance beyond which thermal fluctuations strongly bend the polymer. Electrostatic interactions introduce several competing length scales: the distance, b, between charged phosphates along the ssNA backbone; the distance over which electrostatic fields are screened in salty solution (the Debye length, κ −1 ); and the distance at which interactions between elementary charges in water have energy kB T (the Bjerrum length, lB ).Prior studies have elucidated ssNA elastic behavior in the lowand high-force limits. At low forces, corresponding to tensile lengths larger than κ −1 (i....

show abstract

Section: Discussionmentioning

confidence: 97%

Single-stranded nucleic acid elasticity arises from internal electrostatic tension

Jacobson

McIntosh

Stevens

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since nucleic acids are highly charged polyanions, their native structure formation undergoes strong intramolecule Coulombic repulsions . However, metal ions in the solution can bind to nucleic acids and significantly reduce the Coulombic repulsion, thus favoring the structure folding of nucleic acids (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)13,23,25). Compared with monovalent ions, multivalent ions play a more important and efficient role in structure folding (e.g., Mg 2þ of millimolar concentration can generally induce RNA folding), whereas Na þ can only cause RNA folding at approximately molar concentrations (8,9,.…”

Section: Introductionmentioning

confidence: 99%

“…Compared with monovalent ions, multivalent ions play a more important and efficient role in structure folding (e.g., Mg 2þ of millimolar concentration can generally induce RNA folding), whereas Na þ can only cause RNA folding at approximately molar concentrations (8,9,. More importantly, a nucleic acid generally resides in mixed divalent/monovalent ion solutions (1)(2)(3)(4)(5)(6)(7). Therefore, the competitive binding of divalent and monovalent ions is critical to the structure folding and stability of nucleic acids (8,9,12,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45).…”

Section: Introductionmentioning

confidence: 99%

Competitive Binding of Mg2+ and Na+ Ions to Nucleic Acids: From Helices to Tertiary Structures

Kun

Wang

Xiong

et al. 2018

Biophysical Journal

View full text Add to dashboard Cite

Nucleic acids generally reside in cellular aqueous solutions with mixed divalent/monovalent ions, and the competitive binding of divalent and monovalent ions is critical to the structures of nucleic acids because of their polyanionic nature. In this work, we first proposed a general and effective method for simulating a nucleic acid in mixed divalent/monovalent ion solutions with desired bulk ion concentrations via molecular dynamics (MD) simulations and investigated the competitive binding of Mg/Na ions to various nucleic acids by all-atom MD simulations. The extensive MD-based examinations show that single MD simulations conducted using the proposed method can yield desired bulk divalent/monovalent ion concentrations for various nucleic acids, including RNA tertiary structures. Our comprehensive analyses show that the global binding of Mg/Na to a nucleic acid is mainly dependent on its structure compactness, as well as Mg/Na concentrations, rather than the specific structure of the nucleic acid. Specifically, the relative global binding of Mg over Na is stronger for a nucleic acid with higher effective surface charge density and higher relative Mg/Na concentrations. Furthermore, the local binding of Mg/Na to a phosphate of a nucleic acid mainly depends on the local phosphate density in addition to Mg/Na concentrations.

show abstract

“…Ions, specifically cations, can reduce the electrostatic repulsion, which is referred to as screening (5)(6)(7)(8) and, as importantly, mitigate electrostatic attraction with oppositely charged molecules, such as RNA binding proteins and aminoglycosides (9)(10)(11)(12). Charge screening by ions is greatly affected by the charge of the cation in addition to its bulk concentration (13,14), effects that are manifest in the folding of RNAs upon addition of millimolar Mg 2+ in backgrounds of much higher monovalent cation concentrations (6,(15)(16)(17) While there are important examples of specifically bound ions that are required for RNA folding and function (6,18), the vast majority of interacting ions are dynamically associated in a sheath that surrounds these molecules, referred as the "ion atmosphere" (7,(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Quantitative studies of an RNA duplex electrostatics by ion counting

Gębala

Herschlag

2019

Preprint

View full text Add to dashboard Cite

Ribonucleic acids are one of the most charged polyelectrolytes in nature, and understanding of their electrostatics is fundamental to their structure and biological functions. An effective way to characterize the electrostatic field generated by nucleic acids is to quantify interactions between nucleic acids and ions that surround the molecules. These ions form a loosely associated cloud referred as an ion atmosphere. While theoretical and computational studies can describe the ion atmosphere around RNAs, benchmarks are needed to guide the development of these approaches and experiments to-date that read out RNA-ion interaction are limited. Here we present ion counting studies to quantify the number of ions surrounding well-defined model systems of 24-bp RNA and DNA duplexes. We observe that the RNA duplex attracts more cations and expels fewer anions compared to the DNA duplex and the RNA duplex interacts significantly more strongly with the divalent cation Mg 2+ . These experimental results strongly suggest that the RNA duplex generates a stronger electrostatic field than DNA, as is predicted based on the structural differences between their helices. Theoretical calculations using non-linear Poisson-Boltzmann equation give excellent agreement with experiment for monovalent ions but underestimate Mg 2+ -DNA and Mg 2+ -RNA interactions by 20%. These studies provide needed stringent benchmarks to use against other all-atom theoretical models of RNA-ion interactions, interactions that likely must be well accounted for structurally, dynamically, and energetically to confidently model RNA structure, interactions, and function.

show abstract

Counting the ions surrounding nucleic acids

Cited by 36 publications

References 98 publications

Single-stranded nucleic acid elasticity arises from internal electrostatic tension

Single-stranded nucleic acid elasticity arises from internal electrostatic tension

Competitive Binding of Mg2+ and Na+ Ions to Nucleic Acids: From Helices to Tertiary Structures

Quantitative studies of an RNA duplex electrostatics by ion counting

Contact Info

Product

Resources

About