Electrostatic interactions in biological DNA-related systems

Cherstvy, Andrey G.

doi:10.1039/c0cp02796k

Cited by 163 publications

(160 citation statements)

References 451 publications

(594 reference statements)

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“…1 nN) is high enough to produce significant deformations of the chromatids. As expected for structures with components having large charges on their surfaces [74][75][76], divalent cations cause chromatin [2,22,27] and chromosome [67,73] condensation, but it has been observed [79] that crowding agents such as polyethylene glycol can also compact chromosomes even when the cation concentrations are very low. This suggests that the crowded environment of the cell can generate entropic forces [80] which may also contribute to the recovery of the initial size of deformed chromatids.…”

Section: Discussionmentioning

confidence: 99%

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The energy components of stacked chromatin layers explain the morphology, dimensions and mechanical properties of metaphase chromosomes

Daban

2014

J. R. Soc. Interface.

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The measurement of the dimensions of metaphase chromosomes in different animal and plant karyotypes prepared in different laboratories indicates that chromatids have a great variety of sizes which are dependent on the amount of DNA that they contain. However, all chromatids are elongated cylinders that have relatively similar shape proportions (length to diameter ratio approx. 13). To explain this geometry, it is considered that chromosomes are self-organizing structures formed by stacked layers of planar chromatin and that the energy of nucleosome-nucleosome interactions between chromatin layers inside the chromatid is approximately 3.6 Â 10 220 J per nucleosome, which is the value reported by other authors for internucleosome interactions in chromatin fibres. Nucleosomes in the periphery of the chromatid are in contact with the medium; they cannot fully interact with bulk chromatin within layers and this generates a surface potential that destabilizes the structure. Chromatids are smooth cylinders because this morphology has a lower surface energy than structures having irregular surfaces. The elongated shape of chromatids can be explained if the destabilizing surface potential is higher in the telomeres (approx. 0.16 mJ m 22 ) than in the lateral surface (approx. 0.012 mJ m 22 ). The results obtained by other authors in experimental studies of chromosome mechanics have been used to test the proposed supramolecular structure. It is demonstrated quantitatively that internucleosome interactions between chromatin layers can justify the work required for elastic chromosome stretching (approx. 0.1 pJ for large chromosomes). The high amount of work (up to approx. 10 pJ) required for large chromosome extensions is probably absorbed by chromatin layers through a mechanism involving nucleosome unwrapping.

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Section: Discussionmentioning

confidence: 99%

“…This introduces covalent cross-links into the structure in addition to the electrostatic interactions responsible for histone -DNA and nucleosome-nucleosome associations [74][75][76]. Therefore, as in the case of other soft-matter structures [77], it is better to consider that chromosomes are hydrogels with a liquid crystal organization.…”

Section: Discussionmentioning

confidence: 99%

The energy components of stacked chromatin layers explain the morphology, dimensions and mechanical properties of metaphase chromosomes

Daban

2014

J. R. Soc. Interface.

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“…DNA-ligand binding | DNA packaging | atomic force microscopy | atomistic simulations | Poisson-Boltzmann equation E lectrostatic forces have long been recognized to inherently influence the DNA structure and interactions (1,2) including DNA bending and folding (3,4), DNA packaging (5-7), and DNA-ligand recognition (8)(9)(10), owing to the high charge density of the DNA molecule. In particular, the crucial role of coulombic forces in the binding affinity of molecules to a specific DNA sequence, such as clinically important drugs into minor grooves (9) and protein complexes into major grooves (11), has been well established (12).…”

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confidence: 99%

Direct measurement of the dielectric polarization properties of DNA

Cuervo

Dans

Carrascosa

et al. 2014

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

177

138

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The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy. In contrast to the common assumption of low-polarizable behavior like proteins (e r ∼ 2-4), we found that the DNA dielectric constant is ∼8, considerably higher than the value of ∼3 found for capsid proteins. State-of-the-art molecular dynamic simulations confirm the experimental findings, which result in sensibly decreased DNA interaction free energy than normally predicted by Poisson-Boltzmann methods. Our findings reveal a property at the basis of DNA structure and functions that is needed for realistic theoretical descriptions, and illustrate the synergetic power of scanning probe microscopy and theoretical computation techniques.DNA-ligand binding | DNA packaging | atomic force microscopy | atomistic simulations | Poisson-Boltzmann equation E lectrostatic forces have long been recognized to inherently influence the DNA structure and interactions (1, 2) including DNA bending and folding (3, 4), DNA packaging (5-7), and DNA-ligand recognition (8-10), owing to the high charge density of the DNA molecule. In particular, the crucial role of coulombic forces in the binding affinity of molecules to a specific DNA sequence, such as clinically important drugs into minor grooves (9) and protein complexes into major grooves (11), has been well established (12). However, although detailed knowledge of DNA-DNA and DNA-ligand interactions can nowadays be obtained by high-resolution structural techniques, energetic analysis remains experimentally challenging because it requires quantification of the different contributions to such interactions, in particular the electrostatic energy term.To study the DNA electrostatics, theoretical methods are normally used. All of them require to precisely know the DNA polarization properties in addition to the detailed molecular structure and charge distribution (13-15). In the commonly used mean-field approximation, such as the Poisson-Boltzmann theory, this means including explicitly or implicitly the dielectric constant of DNA, « DNA , a measure of the screening of coulombic forces between charges due to the presence of the DNA molecule. However, despite its crucial impact, the dielectric constant of DNA has remained unknown so far. In the absence of a precise knowledge of « DNA , theoretical models typically assume DNA to be a low-polarizable medium with « DNA ∼ 2-4 like dry proteins surrounded by a highly screening solvent with the dielectric constant of the bulk water ∼80 (13-17). However, this is a simplified picture that lacks experimental validation and introduces a major source of uncertainty, which can give completely biased results in theoretical met...

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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].…”

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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Electrostatic interactions in biological DNA-related systems

Cited by 163 publications

References 451 publications

The energy components of stacked chromatin layers explain the morphology, dimensions and mechanical properties of metaphase chromosomes

The energy components of stacked chromatin layers explain the morphology, dimensions and mechanical properties of metaphase chromosomes

Direct measurement of the dielectric polarization properties of DNA

Molecular Dynamics Simulation of High Density DNA Arrays

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