Molecular Dynamics Simulation of Multivalent-Ion Mediated Attraction between DNA Molecules

Dai, Liang; Mu, Yuguang; Nordenskiöld, Lars; Maarel, Johan R. C. van der

doi:10.1103/physrevlett.100.118301

Cited by 107 publications

(126 citation statements)

References 23 publications

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“…38 Full atomic scale Molecular Dynamics simulations have revealed attractive ion bridges, i.e., multivalent ions which are simultaneously and temporarily bound to opposing DNA duplexes with a lifetime on the order of a few nanoseconds. 39 Furthermore, a small angle neutron scattering (SANS) study of the synthetic poly(styrenesulfonic acid) (PSS) has shown that the chain contracts below the Gaussian chain limit in the presence of calcium counterions. 40 The similarity in behavior of PSS and DNA suggests that the multivalent ion mediated attraction is a general phenomenon pertaining to highly charged linear polyelectrolytes.…”

Section: Effects Of Divalent Saltmentioning

confidence: 99%

Effects of electrostatic screening on the conformation of single DNA molecules confined in a nanochannel

Zhang

Kan

et al. 2008

The Journal of Chemical Physics

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Single T4-DNA molecules were confined in rectangular-shaped channels with a depth of 300 nm and a width in the range 150-300 nm casted in a poly(dimethylsiloxane) nanofluidic chip. The extensions of the DNA molecules were measured with fluorescence microscopy as a function of the ionic strength and composition of the buffer as well as the DNA intercalation level by the YOYO-1 dye. The data were interpreted with scaling theory for a wormlike polymer in good solvent, including the effects of confinement, charge, and self-avoidance. It was found that the elongation of the DNA molecules with decreasing ionic strength can be interpreted in terms of an increase of the persistence length. Self-avoidance effects on the extension are moderate, due to the small correlation length imposed by the channel cross-sectional diameter.Intercalation of the dye results in an increase of the DNA contour length and a partial neutralization of the DNA charge, but besides effects of electrostatic origin it has no significant effect on the bare bending rigidity. In the presence of divalent cations, the DNA molecules were observed to contract, but they do not collapse into a condensed structure. It is proposed that this contraction results from a divalent counterion mediated attractive force between the segments of the DNA molecule.

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Section: Effects Of Divalent Saltmentioning

confidence: 99%

Effects of electrostatic screening on the conformation of single DNA molecules confined in a nanochannel

Zhang

Kan

et al. 2008

The Journal of Chemical Physics

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100

154

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“…One issue is the real nature of the commonly used condensing ions: Cobalt hexammine is a coordination metal complex; spermidine and spermine are chain-like molecules with distributed monocharges. Treating counterions as charged spheres can be flawed (20), though commonly practiced. Furthermore, the grooves of dsDNA can be binding sites for cations, and the exposed polar groups may even coordinate specific counterions (4).…”

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confidence: 99%

Divalent counterion-induced condensation of triple-strand DNA

Qiu

Parsegian

Rau

2010

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

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Understanding and manipulation of the forces assembling DNA/ RNA helices have broad implications for biology, medicine, and physics. One subject of significance is the attractive force between dsDNA mediated by polycations of valence ≥3. Despite extensive studies, the physical origin of the "like-charge attraction" remains unsettled among competing theories. Here we show that triplestrand DNA (tsDNA), a more highly charged helix than dsDNA, is precipitated by alkaline-earth divalent cations that are unable to condense dsDNA. We further show that our observation is general by examining several cations (Mg 2þ , Ba 2þ , and Ca 2þ ) and two distinct tsDNA constructs. Cation-condensed tsDNA forms ordered hexagonal arrays that redissolve upon adding monovalent salts. Forces between tsDNA helices, measured by osmotic stress, follow the form of hydration forces observed with condensed dsDNA. Probing a well-defined system of point-like cations and tsDNAs with more evenly spaced helical charges, the counterintuitive observation that the more highly charged tsDNA (vs. dsDNA) is condensed by cations of lower valence provides new insights into theories of polyelectrolytes and the biological and pathological roles of tsDNA. Cations and tsDNAs also hold promise as a model system for future studies of DNA-DNA interactions and electrostatic interactions in general.DNA condensation | small angle X-ray diffraction H ighly charged DNA helices naturally repel each other under physiological conditions (1). However, cations of valence ≥3 very effectively condense DNA at micromolar concentrations (2). The most studied systems are the condensation of dsDNA with cobalt 3þ hexammine and the biogenic polyamines (spermidine 3þ and spermine 4þ ), whereas polymer-based cations are being exploited as DNA packaging agents for gene delivery (3). In contrast, nonspecifically interacting monovalent and divalent cations [i.e., excluding base-coordinating transition-metal ions (4) such as Mn 2þ , Ni 2þ , and Cu 2þ ], even at molar concentrations, do not condense dsDNA from dilute solution (2). The prominent role of cation valence has promoted electrostatic interaction as the primary candidate to explain this multivalent cation mediated DNA-DNA attraction (1). Whereas it is clear that further considerations must be made beyond the mean field PoissonBoltzmann (PB) treatment, which always predicts like-charge repulsion, the physical basis for DNA condensation is still under intensive debate (5).The multifaceted nature of DNA-ion interactions and of possible DNA-ion-DNA correlations between apposing helices has led to theories that differ greatly in starting assumptions. For instance, counterions have been treated either as continuous ionic "clouds" or as discrete point-like cations of finite radius; the DNA helix has been modeled as a continuously charged rod or to have discretely charged phosphates placed on a helical path around a smooth rod. As a result, a number of competing theories have been proposed to explain cation mediated DNA-DNA attraction....

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“…While the continuum approaches which mostly underpin the theoretical endeavors described in the paragraph above led to important insights, e.g., the significance of counterion correlations in reversing the sign of the electrostatic interactions between charged helices, backed up by detailed coarse grained simulations [41][42][43][44][45] the molecular details of the DNA solution exposed surface, the granularity of the molecular solvent, and the complicated interactions between both and the mobile charges in solution, preclude the understanding of all the relevant details. As a consequence, detailed all-atom molecular dynamics (MD) simulations appear to be the only vehicle that can bring forth a deeper understanding of the mechanisms and the relevant couplings between them [46], leading to the experimentally observed interaction and ordering phenomenology of DNA in high density mesophases [47][48][49][50][51]. On the downside, all-atom MD simulations of such complicated systems require huge computational resources and the majority of simulations aiming to describe details of the DNA solution phenomenology consist of 1-3 DNA molecules, where the focus is the counterion binding [48,52] and azimuthal dependence of DNA-DNA interaction [49].…”

Section: Simulating Dna Arraysmentioning

confidence: 99%

“…As a consequence, detailed all-atom molecular dynamics (MD) simulations appear to be the only vehicle that can bring forth a deeper understanding of the mechanisms and the relevant couplings between them [46], leading to the experimentally observed interaction and ordering phenomenology of DNA in high density mesophases [47][48][49][50][51]. On the downside, all-atom MD simulations of such complicated systems require huge computational resources and the majority of simulations aiming to describe details of the DNA solution phenomenology consist of 1-3 DNA molecules, where the focus is the counterion binding [48,52] and azimuthal dependence of DNA-DNA interaction [49]. Only recently it became feasible to set up an all-atom MD simulation for a larger set of DNA molecules [51,53] characterized by a single packing geometry with only a partial characterization of the DNA countercharge and solvent ordering.…”

Section: Simulating Dna Arraysmentioning

confidence: 99%

Molecular Dynamics Simulation of High Density DNA Arrays

2018

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Densely packed DNA arrays exhibit hexagonal and orthorhombic local packings, as well as a weakly first order transition between them. While we have some understanding of the interactions between DNA molecules in aqueous ionic solutions, the structural details of its ordered phases and the mechanism governing the respective phase transitions between them remains less well understood. Since at high DNA densities, i.e., small interaxial spacings, one can neither neglect the atomic details of the interacting macromolecular surfaces nor the atomic details of the intervening ionic solution, the atomistic resolution is a sine qua non to properly describe and analyze the interactions between DNA molecules. In fact, in order to properly understand the details of the observed osmotic equation of state, one needs to implement multiple levels of organization, spanning the range from the molecular order of DNA itself, the possible ordering of counterions, and then all the way to the induced molecular ordering of the aqueous solvent, all coupled together by electrostatic, steric, thermal and direct hydrogen-bonding interactions. Multiscale simulations therefore appear as singularly suited to connect the microscopic details of this system with its macroscopic thermodynamic behavior. We review the details of the simulation of dense atomistically resolved DNA arrays with different packing symmetries and the ensuing osmotic equation of state obtained by enclosing a DNA array in a monovalent salt and multivalent (spermidine) counterions within a solvent permeable membrane, mimicking the behavior of DNA arrays subjected to external osmotic stress. By varying the DNA density, the local packing symmetry, and the counterion type, we are able to analyze the osmotic equation of state together with the full structural characterization of the DNA subphase, the counterion distribution and the solvent structural order in terms of its different order parameters and consequently identify the most important contribution to the DNA-DNA interactions at high DNA densities.

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Molecular Dynamics Simulation of Multivalent-Ion Mediated Attraction between DNA Molecules

Cited by 107 publications

References 23 publications

Effects of electrostatic screening on the conformation of single DNA molecules confined in a nanochannel

Effects of electrostatic screening on the conformation of single DNA molecules confined in a nanochannel

Divalent counterion-induced condensation of triple-strand DNA

Molecular Dynamics Simulation of High Density DNA Arrays

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