Unwrapping of Nucleosomal DNA Ends: A Multiscale Molecular Dynamics Study

Voltz, Karine; Trylska, Joanna; Calimet, Nicolas; Smith, Jeremy C.; Langowski, Jörg

doi:10.1016/j.bpj.2011.11.4028

Cited by 64 publications

(65 citation statements)

References 52 publications

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“…Accessibility to the DNA is critical for gene transcription, and therefore, the unwrapping of nucleosome DNA from the histone core has been extensively studied both experimentally (86) and computationally (87). Experiments have previously shown that at high pH, there is a loosening of the nucleosome structure (88).…”

Section: Nucleosome Dna Unwrappingmentioning

confidence: 98%

Speed of Conformational Change: Comparing Explicit and Implicit Solvent Molecular Dynamics Simulations

Anandakrishnan

Drozdetski

Walker

et al. 2015

Biophysical Journal

172

192

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Adequate sampling of conformation space remains challenging in atomistic simulations, especially if the solvent is treated explicitly. Implicit-solvent simulations can speed up conformational sampling significantly. We compare the speed of conformational sampling between two commonly used methods of each class: the explicit-solvent particle mesh Ewald (PME) with TIP3P water model and a popular generalized Born (GB) implicit-solvent model, as implemented in the AMBER package. We systematically investigate small (dihedral angle flips in a protein), large (nucleosome tail collapse and DNA unwrapping), and mixed (folding of a miniprotein) conformational changes, with nominal simulation times ranging from nanoseconds to microseconds depending on system size. The speedups in conformational sampling for GB relative to PME simulations, are highly system- and problem-dependent. Where the simulation temperatures for PME and GB are the same, the corresponding speedups are approximately onefold (small conformational changes), between ∼1- and ∼100-fold (large changes), and approximately sevenfold (mixed case). The effects of temperature on speedup and free-energy landscapes, which may differ substantially between the solvent models, are discussed in detail for the case of miniprotein folding. In addition to speeding up conformational sampling, due to algorithmic differences, the implicit solvent model can be computationally faster for small systems or slower for large systems, depending on the number of solute and solvent atoms. For the conformational changes considered here, the combined speedups are approximately twofold, ∼1- to 60-fold, and ∼50-fold, respectively, in the low solvent viscosity regime afforded by the implicit solvent. For all the systems studied, 1) conformational sampling speedup increases as Langevin collision frequency (effective viscosity) decreases; and 2) conformational sampling speedup is mainly due to reduction in solvent viscosity rather than possible differences in free-energy landscapes between the solvent models.

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Section: Nucleosome Dna Unwrappingmentioning

confidence: 98%

Speed of Conformational Change: Comparing Explicit and Implicit Solvent Molecular Dynamics Simulations

Anandakrishnan

Drozdetski

Walker

et al. 2015

Biophysical Journal

172

192

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show abstract

“…DNA was coarse-grained into two chains of sites representing the phosphate groups with bond-only interactions in between them. A recent all-atom simulation of a single NCP applied Boltzmann inversion to obtain effective potentials that were used in a CG NCP simulation [40,51], but as it is based on the Boltzmann inversion, it is of limited value for treating long-range electrostatic interactions [52].…”

Section: Introductionmentioning

confidence: 99%

A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

et al. 2014

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Abstract:Computer modeling of very large biomolecular systems, such as long DNA polyelectrolytes or protein-DNA complex-like chromatin cannot reach all-atom resolution in a foreseeable future and this necessitates the development of coarse-grained (CG) approximations. DNA is both highly charged and mechanically rigid semi-flexible polymer and adequate DNA modeling requires a correct description of both its structural stiffness and salt-dependent electrostatic forces. Here, we present a novel CG model of DNA that approximates the DNA polymer as a chain of 5-bead units. Each unit represents two DNA base pairs with one central bead for bases and pentose moieties and four others for phosphate groups. Charges, intra-and inter-molecular force field potentials for the CG DNA model were calculated using the inverse Monte Carlo method from all atom molecular dynamic (MD) simulations of 22 bp DNA oligonucleotides. The CG model was tested by performing dielectric continuum Langevin MD simulations of a 200 bp double helix DNA in solutions of monovalent salt with explicit ions. Excellent agreement with experimental data was obtained for the dependence of the DNA persistent length on salt concentration in the range 0.1-100 mM. The new CG DNA model is suitable for modeling various biomolecular systems with adequate description of electrostatic and mechanical properties.

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“…A number of experimental [30][31][32][33], theoretical [34][35][36], and computer simulation studies [37][38][39][40][41][42][43][44][45] have emerged on this subject in recent years. Chromatin 30-nm fibers interact electrostatically with each other via "contacting" NCPs positioned on the fiber periphery, both in canonical solenoidal [46,47] and crosslinked [34] fiber models.…”

Section: Interactions Between the Chromatin Fibersmentioning

confidence: 99%

Structure-driven homology pairing of chromatin fibers: the role of electrostatics and protein-induced bridging

Cherstvy

Teif

2013

J Biol Phys

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Chromatin domains formed in vivo are characterized by different types of 3D organization of interconnected nucleosomes and architectural proteins. Here, we quantitatively test a hypothesis that the similarities in the structure of chromatin fibers (which we call "structural homology") can affect their mutual electrostatic and protein-mediated bridging interactions. For example, highly repetitive DNA sequences in heterochromatic regions can position nucleosomes so that preferred inter-nucleosomal distances are preserved on the surfaces of neighboring fibers. On the contrary, the segments of chromatin fiber formed on unrelated DNA sequences have different geometrical parameters and lack structural complementarity pivotal for stable association and cohesion. Furthermore, specific functional elements such as insulator regions, transcription start and termination sites, and replication origins are characterized by strong nucleosome ordering that might induce structure-driven iterations of chromatin fibers. We propose that shape-specific protein-bridging interactions facilitate long-range pairing of chromatin fragments, while for closely-juxtaposed fibers electrostatic forces can in addition yield fine-tuned structurespecific recognition and pairing. These pairing effects can account for some features observed for mitotic and inter-phase chromatins.

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Unwrapping of Nucleosomal DNA Ends: A Multiscale Molecular Dynamics Study

Cited by 64 publications

References 52 publications

Speed of Conformational Change: Comparing Explicit and Implicit Solvent Molecular Dynamics Simulations

Speed of Conformational Change: Comparing Explicit and Implicit Solvent Molecular Dynamics Simulations

A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

Structure-driven homology pairing of chromatin fibers: the role of electrostatics and protein-induced bridging

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