Spatial Distribution of Competing Ions around DNA in Solution

Andresen, Kurt; Das, Rhiju; Park, Hye Yoon; Smith, Harold H.; Kwok, Lisa W.; Lamb, Jessica S.; Kirkland, Earl J.; Herschlag, Dan; Finkelstein, K. D.; Pollack, Lois

doi:10.1103/physrevlett.93.248103

Cited by 113 publications

(121 citation statements)

References 26 publications

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“…Thus, the recent ability to decipher the shape of this atmosphere by anomalous small angle x-ray scattering provided an unusually direct experimental window into properties of the atmosphere [56,57]. Further, the contents of the atmosphere have recently been quantitatively dissected, by essentially counting the ions associated with a nucleic acid under a variety of ionic conditions.…”

Section: Simple Forces Underlying the Complex Behavior Of Rnamentioning

confidence: 99%

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Chu

Herschlag

2008

Current Opinion in Structural Biology

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SummaryThe rapid development of our understanding of the diverse biological roles fulfilled by non-coding RNA has motivated interest in the basic macromolecular behavior, structure, and function of RNA. We focus on two areas in the behavior of complex RNAs. First, we present advances in the understanding of how RNA folding is accomplished in vivo by presenting a mechanism for the action of DEAD-box proteins. Members of this family are intimately associated with almost all cellular processes involving RNA, mediating RNA structural rearrangements and chaperoning their folding. Next, we focus on advances in understanding and characterizing the basic biophysical forces that govern the folding of complex RNAs. Ultimately we expect that a confluence and synergy between these approaches will lead to profound understanding of RNA and its biology.The explosion in our knowledge about noncoding RNA (ncRNA) -RNA that is not translated into protein -has expanded interest in RNA beyond the traditional RNA community. Diverse ncRNAs include the recently-discovered riboswitches, whose novel gene-regulation function is induced by the binding of small metabolites [1]; most of the so-called "Human Accelerated Regions" (HAR) of the human genome, whose recent evolution may be linked to the emergence of the human brain [2]; and many ncRNAs of unknown function [3]. These discoveries underscore the need to understand the fundamental macromolecular behavior of RNA, its structure and dynamics, and how these RNAs are handled and exploited in biology.Study of catalytic RNAs, which allow detection of correct folding via activity measurements, has established basic thermodynamic and kinetic properties of RNA folding. Large catalytic RNAs such as the group I intron from Tetrahymena thermophila and the RNase P RNA from Bacillus subtilis fold at vastly different rates under different conditions upon addition of Mg 2+ and have been shown to fold via multiple parallel pathways, in which different molecules follow different routes with different rates and intermediates, to a common final folded structure [4,5]. These observations support the common view that RNAs traverse rugged energy landscapes as they fold [6,7]. However, little is known about the true shape of these

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Section: Simple Forces Underlying the Complex Behavior Of Rnamentioning

confidence: 99%

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Chu

Herschlag

2008

Current Opinion in Structural Biology

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“…Thus, our experiments identify the degree of importance of and quantitate a fundamental limitation in NLPB theory. As size effects modulate electrostatic screening and thus the conformation and stability of nucleic acids and their complexes 41,42,50 , adequate treatments of the size effect in electrostatic models are necessary for an in-depth understanding of nucleic acid thermodynamics.…”

Section: Competitive Association Of Cations: Assessing the Effects Ofmentioning

confidence: 99%

Quantitative and Comprehensive Decomposition of the Ion Atmosphere around Nucleic Acids

et al. 2007

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The ion atmosphere around nucleic acids critically affects biological and physical processes such as chromosome packing, RNA folding, and molecular recognition. However, the dynamic nature of the ion atmosphere renders it difficult to characterize. The basic thermodynamic description of this atmosphere, a full accounting of the type and number of associated ions, has remained elusive. Here we provide the first complete accounting of the ion atmosphere, using buffer equilibration and atomic emission spectroscopy (BE-AES) to accurately quantitate the cation association and anion depletion. We have examined the influence of ion size and charge on ion occupancy around simple, well-defined DNA molecules. The relative affinity of monovalent and divalent cations correlates inversely with their size. Divalent cations associate preferentially over monovalent cations; e.g., with Na + in four-fold excess of Mg 2+ (20 vs. 5 mM), the ion atmosphere nevertheless has three-fold more Mg 2+ than Na + . Further, the dicationic polyamine putrescine 2+ does not compete effectively for association relative to divalent metal ions, presumably because of its lower charge density. These and other BE-AES results can be used to evaluate and guide the improvement of electrostatic treatments. As a first step, we compare the BE-AES results to predictions from the widely-used nonlinear Poisson Boltzmann (NLPB) theory and assess the applicability and precision of this theory. In the future, BE-AES in conjunction with improved theoretical models, can be applied to complex binding and folding equilibria of nucleic acids and their complexes, to parse the electrostatic contribution from the overall thermodynamics of important biological processes.

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“…Differential ion size however does play a role in electrostatics interactions; this was recently shown for DNA in solutions containing competing cations. 35 Coalson and co-workers [36][37][38] as well as Orland and co-workers 25 developed an attractive solution to the problem of the influence of ion size using a lattice field theory. This solution was recently generalized by Chu et al 26 to deal with ions with two different sizes; it is referred to as the SMPB theory which we describe below.…”

Section: B Size Modified Poisson-boltzmann Equationmentioning

confidence: 99%

AQUASOL: An efficient solver for the dipolar Poisson–Boltzmann–Langevin equation

Koehl

Delarue

2010

The Journal of Chemical Physics

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The Poisson-Boltzmann ͑PB͒ formalism is among the most popular approaches to modeling the solvation of molecules. It assumes a continuum model for water, leading to a dielectric permittivity that only depends on position in space. In contrast, the dipolar Poisson-Boltzmann-Langevin ͑DPBL͒ formalism represents the solvent as a collection of orientable dipoles with nonuniform concentration; this leads to a nonlinear permittivity function that depends both on the position and on the local electric field at that position. The differences in the assumptions underlying these two models lead to significant differences in the equations they generate. The PB equation is a second order, elliptic, nonlinear partial differential equation ͑PDE͒. Its response coefficients correspond to the dielectric permittivity and are therefore constant within each subdomain of the system considered ͑i.e., inside and outside of the molecules considered͒. While the DPBL equation is also a second order, elliptic, nonlinear PDE, its response coefficients are nonlinear functions of the electrostatic potential. Many solvers have been developed for the PB equation; to our knowledge, none of these can be directly applied to the DPBL equation. The methods they use may adapt to the difference; their implementations however are PBE specific. We adapted the PBE solver originally developed by Holst and Saied ͓J. Comput. Chem. 16, 337 ͑1995͔͒ to the problem of solving the DPBL equation. This solver uses a truncated Newton method with a multigrid preconditioner. Numerical evidences suggest that it converges for the DPBL equation and that the convergence is superlinear. It is found however to be slow and greedy in memory requirement for problems commonly encountered in computational biology and computational chemistry. To circumvent these problems, we propose two variants, a quasi-Newton solver based on a simplified, inexact Jacobian and an iterative self-consistent solver that is based directly on the PBE solver. While both methods are not guaranteed to converge, numerical evidences suggest that they do and that their convergence is also superlinear. Both variants are significantly faster than the solver based on the exact Jacobian, with a much smaller memory footprint. All three methods have been implemented in a new code named AQUASOL, which is freely available.

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Spatial Distribution of Competing Ions around DNA in Solution

Cited by 113 publications

References 26 publications

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Quantitative and Comprehensive Decomposition of the Ion Atmosphere around Nucleic Acids

AQUASOL: An efficient solver for the dipolar Poisson–Boltzmann–Langevin equation

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