Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation

Sutthibutpong, Thana; Matek, Christian; Benham, Craig J.; Slade, Gabriel Gouvêa; Noy, Agnes; Laughton, Charles A.; Doye, Jonathan P. K.; Louis, Ard A.; Harris, Sarah A.

doi:10.1093/nar/gkw815

Cited by 57 publications

(73 citation statements)

References 58 publications

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“…The four DNA sequences chosen for this study ((AA)12, (AT)12, (GG)12 and (CG)12) enable us to interrogate not only the impact of the overall GC/AT ratio but also the impact of the bp-order, which causes different strengths on stacking interactions, being these critical for DNA stability. Overall, ATrich sequences show higher propensity to melt compared with CG-rich sequences in agreement with previous studies [15], [23], [24], [36], although striking differences are found whether sequences contain RY and YR intra-strand stacking or YY and RR. Poly-d(C) appears to be significantly more resistant than the other G-rich sequence, polyd(CG), because the former is the sole sequence that do not form melting bubbles for any supercoiling density, and the latter presents denaturation for all torsional constraints.…”

Section: Discussionsupporting

confidence: 92%

“…The effect of torque on simulated linear DNA structures has been relatively underexplored in comparison. By imposing torsional constraints, simulations have shown that unwounded DNA has a greater predisposition to form melting bubbles compared to relaxed DNA, with this propensity being strongly dependent on sequence: denaturation was only observed on an (AT)3 segment in linear DNA [23] and prominently in AT-rich areas in undertwisted small DNA circles between 60-110 bp [24]. Modelling an infinite linear tract of DNA upon undertwisting showed that DNA partitions its perturbations such that there are regions of extreme disruption in coexistence with regions which remain relatively close to the canonical B-form DNA structure, and that this is sequence-dependent [25].…”

Section: Introductionmentioning

confidence: 99%

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The emergence of sequence-dependent structural motifs in stretched, torsionally constrained DNA

Shepherd

Greenall

Probert

et al. 2019

Preprint

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The double-helical structure of DNA results from canonical base pairing and stacking interactions.However, variations from steady-state conformations result from mechanical perturbations in cells.These different topologies have physiological relevance but their dependence on sequence remains unclear. Here, we use molecular dynamics simulations to show that sequence differences result in markedly different structural motifs upon physiological twisting and stretching. We simulated overextension on four different sequences of DNA ((AA)12, (AT)12, (GG)12 and (GC)12) with supercoiling densities within the physiological range. We found that DNA denatures in the majority of stretching simulations, surprisingly including those with overtwisted DNA. GC-rich sequences were observed to be more stable than AT-rich, with the specific response dependent on base pair ordering. Furthermore, we found that (AT)12 forms stable periodic structures with noncanonical hydrogen bonds in some regions and non-canonical stacking in others, whereas (GC)12 forms a stacking motif of four base pairs independent of supercoiling density. Our results demonstrate that 20-30% DNA extension is sufficient for breaking B-DNA around and significantly above cellular supercoiling, and that the DNA sequence is crucial for understanding structural changes under mechanical stress. Our findings have important implications for the activities of protein machinery interacting with DNA in all cells.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

The emergence of sequence-dependent structural motifs in stretched, torsionally constrained DNA

Shepherd

Greenall

Probert

et al. 2019

Preprint

Self Cite

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“…There is a good overall agreement between the direct computation of the persistence lengths and Eqs. (18) and (19) (with the plateau values of Fig. 4), for both oxDNA1 and oxDNA2.…”

Section: Stiffness Matrixmentioning

confidence: 78%

DNA elasticity from coarse-grained simulations: The effect of groove asymmetry

Skoruppa

Laleman

Nomidis

et al. 2017

The Journal of Chemical Physics

121

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It is well-established that many physical properties of DNA at sufficiently long length scales can be understood by means of simple polymer models. One of the most widely used elasticity models for DNA is the twistable wormlike chain (TWLC), which describes the double helix as a continuous elastic rod with bending and torsional stiffness. An extension of the TWLC, which has recently received some attention, is the model by Marko and Siggia, who introduced an additional twist-bend coupling, expected to arise from the groove asymmetry. By performing computer simulations of two available versions of oxDNA, a coarsegrained model of nucleic acids, we investigate the microscopic origin of twist-bend coupling. We show that this interaction is negligible in the oxDNA version with symmetric grooves, while it appears in the oxDNA version with asymmetric grooves. Our analysis is based on the calculation of the covariance matrix of equilibrium deformations, from which the stiffness parameters are obtained. The estimated twist-bend coupling coefficient from oxDNA simulations is G = 30 ± 1 nm. The groove asymmetry induces a novel twist length scale and an associated renormalized twist stiffness κ t ≈ 80 nm, which is different from the intrinsic torsional stiffness C ≈ 110 nm. This naturally explains the large variations on experimental estimates of the intrinsic stiffness performed in the past.

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“…Even though these models and tools are generally implemented as freely available and open software packages, the burden of passing from one representation to the other is typically on the end user, making the process not only laborious but also prone to errors. In addition, the lack of interoperability hinders the wider adoption of each model or simulation tool and is especially detrimental to researchers interested in multiscale modeling spanning multiple spatial and temporal scales …”

Section: Introductionmentioning

confidence: 99%

TacoxDNA: A user‐friendly web server for simulations of complex DNA structures, from single strands to origami

et al. 2019

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Simulations of nucleic acids at different levels of structural details are increasingly used to complement and interpret experiments in different fields, from biophysics to medicine and materials science. However, the various structural models currently available for DNA and RNA and their accompanying suites of computational tools can be very rarely used in a synergistic fashion. The tacoxDNA webserver and standalone software package presented here are a step toward a long‐sought interoperability of nucleic acids models. The webserver offers a simple interface for converting various common input formats of DNA structures and setting up molecular dynamics (MD) simulations. Users can, for instance, design DNA rings with different topologies, such as knots, with and without supercoiling, by simply providing an XYZ coordinate file of the DNA centre‐line. More complex DNA geometries, as designable in the cadnano, CanDo and Tiamat tools, can also be converted to all‐atom or oxDNA representations, which can then be used to run MD simulations. Though the latter are currently geared toward the native and LAMMPS oxDNA representations, the open‐source package is designed to be further expandable. TacoxDNA is available at http://tacoxdna.sissa.it. © 2019 Wiley Periodicals, Inc.

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Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation

Cited by 57 publications

References 58 publications

The emergence of sequence-dependent structural motifs in stretched, torsionally constrained DNA

The emergence of sequence-dependent structural motifs in stretched, torsionally constrained DNA

DNA elasticity from coarse-grained simulations: The effect of groove asymmetry

TacoxDNA: A user‐friendly web server for simulations of complex DNA structures, from single strands to origami

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