The Stretched Intermediate Model of B-Z DNA Transition

Lim, Wilber; Feng, Yuan Ping

doi:10.1529/biophysj.104.052027

Cited by 20 publications

(26 citation statements)

References 40 publications

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“…The mechanism along the solid line LFEP path in the free energy landscape essentially corresponds to that proposed by Lim and Feng (19,26) and Kastenholz et al (24). The main features of the model are the formation of a stretched intermediate conformation with parallel phosphate backbones, and the refolding of this intermediate structure into Z-DNA.…”

Section: Discussionsupporting

confidence: 70%

“…Lim and Feng (19,26) used stochastic difference equations (which find the minimum potential path based on the principle of minimum action) to look at the heptamer duplex d(GCGCGCG) [same as d(CGCGCGC)] in implicit solvent (19); Kastenholz et al (24) used targeted molecular dynamics (TMD) to look at the hexamer d(GCGCGC) in explicit water; and Lee et al (25) used TMD and umbrella sampling to study the propagation of a single step in the nanomer d(GCGCGCGCG) [same as d(CGCGCGCGC)] also in explicit solvent. In a similar fashion, we considered various oligomers in aqueous solution formed by traditional bases (not chemically modified) and ignored interactions with other molecules.…”

Section: Discussionmentioning

confidence: 99%

“…This could be partly due to the disruption of the WC base pairs. In addition, (19) (that uses the same force field and implicit solvent) represents a solution to a zero-temperature pathway, whereas (24) (which measures barriers of about 30 kcal/mol for the 4 M solution and 36 kcal/mol for the 0 M solution, for an hexadecamer) could suffer from inaccuracies in the force field or the TMD algorithm (because the numbers do not agree with experimental numbers). It is interesting that in a seemingly different context, our observations from the -based simulations are in line with the conclusions (61) from recent experimental studies that there are two competing modes of over-stretching for a DNA with free ends: (i) formation of a S-DNA, associated with a reversible fast dynamics and (ii) unpeeling of one strand from the other starting from one end, associated with an irreversible slow dynamics.…”

Section: Discussionmentioning

confidence: 99%

“…The methodology of these studies varied from the use of stochastic difference equations (19,22), to dynamic phase diagrams (23) and, most notably, large-scale atomistic molecular dynamics (MD) simulations (24,25). The initial investigations (19,24,26) proposed yet another model for the B–Z-DNA transition that involves the simultaneous formation of a stretched intermediate conformation with parallel phosphate backbones, the transient disruption of the WC hydrogen bond pairing, base flipping and the re-ordering into Z-DNA. In contrast, Lee et al (25) carried out an explicit solvent simulation of the mechanism proposed by Ha et al (21).…”

Section: Introductionmentioning

confidence: 99%

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Reaction path ensemble of the B–Z-DNA transition: a comprehensive atomistic study

Moradi

Babin

Roland

et al. 2012

Nucleic Acids Research

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Since its discovery in 1979, left-handed Z-DNA has evolved from an in vitro curiosity to a challenging DNA structure with crucial roles in gene expression, regulation and recombination. A fundamental question that has puzzled researchers for decades is how the transition from B-DNA, the prevalent right-handed form of DNA, to Z-DNA is accomplished. Due to the complexity of the B–Z-DNA transition, experimental and computational studies have resulted in several different, apparently contradictory models. Here, we use molecular dynamics simulations coupled with state-of-the-art enhanced sampling techniques operating through non-conventional reaction coordinates, to investigate the B–Z-DNA transition at the atomic level. Our results show a complex free energy landscape, where several phenomena such as over-stretching, unpeeling, base pair extrusion and base pair flipping are observed resulting in interconversions between different DNA conformations such as B-DNA, Z-DNA and S-DNA. In particular, different minimum free energy paths allow for the coexistence of different mechanisms (such as zipper and stretch–collapse mechanisms) that previously had been proposed as independent, disconnected models. We find that the B–Z-DNA transition—in absence of other molecular partners—can encompass more than one mechanism of comparable free energy, and is therefore better described in terms of a reaction path ensemble.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reaction path ensemble of the B–Z-DNA transition: a comprehensive atomistic study

Moradi

Babin

Roland

et al. 2012

Nucleic Acids Research

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“…A number of molecular mechanisms have been proposed for the B-Z transition. [31] There is no spectroscopic support for intermediates in three models, the Saenger-Heinemann model, [32] the stretched model, [33] and the zipper model, [34] probably owing to the short lifetime of the intermediates. Goto et al successfully observed an intermediate, designated as B Ã -DNA, in the B-Z transition induced under high salt conditions using a stopped-flow apparatus.…”

Section: Discussionmentioning

confidence: 99%

B–Z DNA Transition Triggered by a Cationic Comb‐Type Copolymer

Shimada

Kano

Maruyama

2009

Adv Funct Materials

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The conformational transition from right‐handed B–DNA to left‐handed Z–DNA—the B–Z transition—has received increased attention recently because of its potential roles in biological systems and its applicability to bionanotechnology. Though the B–Z transition of poly(dG–dC) · poly(dG–dC) is inducible under high salt concentration conditions (over 4 M NaCl) or by addition of multivalent cations, such as hexaamminecobalt(III), no cationic polymer were known to induce the transition. In this study, it is shown by circular dichroism and UV spectroscopy that the cationic comb‐type copolymer, poly(L‐lysine)‐graft‐dextran, but not poly(L‐lysine) homopolymer or a basic peptide, induces the B–Z transition of poly(dG–dC) · poly(dG–dC). At a cationic amino group concentration of 10−4 M the copolymer stabilizes Z–DNA. The transition pathway from the B to the Z form is different to that observed previously. We speculate that the cationic backbone of the copolymer, which reduces electrostatic repulsion among DNA phosphate groups, and the hydrophilic dextran chains, which reduce activity of water, cooperate to induce the B–Z transition. The copolymer specifically modified the micro‐environment around DNA molecules to induce Z–DNA formation through stable and spontaneous inter‐polyelectrolyte complex formation.

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Applying the stochastic difference equation to DNA conformational transitions: A study of B–Z and B–A DNA transitions

Lim

Feng

2005

Biopolymers

Self Cite

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Despite the existence of numerous models to account for the B-Z DNA transition, experimenters have not yet arrived at a conclusive answer to the structural and dynamical features of the B-Z transition. By applying the stochastic difference equation to simulate the B-Z DNA transition, we have shown that the stretched intermediate model of the B-Z transition is more probable than other B-Z transition models such as the Harvey model. This is accomplished by comparing potential energy profiles of various B-Z DNA transition models and calculating relative probabilities based on the stochastic difference equation with respect to length (SDEL) formalism. The results garnered in this article allow for new approaches in determining the structural transition of B-DNA to Z-DNA experimentally. We have also simulated the B-A DNA transition using the stochastic difference equation. Unlike the B-Z DNA transition, the mechanism for the B-A DNA transition is well established. The variation in the pseudorotation angle during the transition is in good agreement with experimental results. Qualitative features of the simulated B-A transition also agree well with experimental data. The SDEL approach is thus a suitable numerical technique to compute long-time molecular dynamics trajectory for DNA molecules.

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The Stretched Intermediate Model of B-Z DNA Transition

Cited by 20 publications

References 40 publications

Reaction path ensemble of the B–Z-DNA transition: a comprehensive atomistic study

Reaction path ensemble of the B–Z-DNA transition: a comprehensive atomistic study

B–Z DNA Transition Triggered by a Cationic Comb‐Type Copolymer

Applying the stochastic difference equation to DNA conformational transitions: A study of B–Z and B–A DNA transitions

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