Monte Carlo approach to the analysis of the rotational diffusion of wormlike chains

Hagerman, Paul J.; Zimm, Bruno H.

doi:10.1002/bip.1981.360200709

Cited by 265 publications

(243 citation statements)

References 40 publications

(20 reference statements)

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“…Correspondingly, DNA conformational properties are well described by the worm-like chain (WLC) model (3). Calculations based on this model accurately reproduce experimental data on hydrodynamic properties of DNA molecules (4)(5)(6), equilibrium distributions of topological states (7)(8)(9)(10)(11)(12), and light and neutron scattering data on supercoiled DNA (13)(14)(15)(16). One of the most impressive tests of the WLC model was the single-molecule measurement of DNA extension under the action of a force applied to the ends of the double helix (17).…”

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confidence: 64%

Cyclization of short DNA fragments and bending fluctuations of the double helix

Smith

Shiffeldrim

et al. 2005

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

244

325

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In an effort to resolve this discrepancy, we tried modifying the theory. We investigated how the distribution of the angles between adjacent base pairs of the double helix affects the cyclization efficiency. We found that only the incorporation of sharp kinks in the angle distribution provides the desired increase of the cyclization efficiency. We did not find a model, however, that fits all cyclization data for DNA fragments of different lengths. Therefore, we carefully reinvestigated the cyclization of 100-bp DNA fragments experimentally and found their cyclization efficiency to be in remarkable agreement with the traditional model of DNA bending. We also found an explanation for the discrepancy between our results and those of Cloutier and Widom.DNA bending ͉ DNA cyclization ͉ DNA flexibility ͉ DNA kinks T he flexibility of the DNA double helix is extremely important for its functioning and has been studied for nearly 50 years (reviewed in ref. 1). It is now generally accepted that the major mechanisms of DNA bending are the small fluctuations between the planes of adjacent base pairs (2). Correspondingly, DNA conformational properties are well described by the worm-like chain (WLC) model (3). Calculations based on this model accurately reproduce experimental data on hydrodynamic properties of DNA molecules (4-6), equilibrium distributions of topological states (7-12), and light and neutron scattering data on supercoiled DNA (13-16). One of the most impressive tests of the WLC model was the single-molecule measurement of DNA extension under the action of a force applied to the ends of the double helix (17). Initially, Bustamante and coworkers (17) tried to fit the experimental results by applying the theory for a freely jointed chain, the only theory being considered at that time, but found a large discrepancy between theoretical and experimental results for large extensions of the molecule. It was soon understood that the WLC model gives a different result in the case of large extensions. The force-extension dependence for the WLC was found to be in excellent agreement with the experimental data (18,19).Theoretical analysis and computations based on the WLC also accurately predict the cyclization efficiency of small DNA fragments, 200-350 bp in length (20-24). For even shorter fragments, this model predicts a very low efficiency of cyclization, and until recently, quantitative measurements of this efficiency had not been attempted. Therefore, it was a complete surprise when Cloutier and Widom (hereafter referred as CW) reported that DNA fragments of Ϸ100 bp in length are cyclized several orders of magnitude more efficiently than the current theory predicts (25). It is known, on the other hand, that microscopically different models of polymer chains can give similar or even identical results for many properties. So, even excellent agreement between a model prediction and a set of experimental data does not necessary mean that the model provides an adequate microscopic description of polymer flexibility. The d...

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mentioning

confidence: 64%

Cyclization of short DNA fragments and bending fluctuations of the double helix

Smith

Shiffeldrim

et al. 2005

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

244

325

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“…We use a series of simulations with varying ratios L͞l P (16,17). The polymer chain is divided into segments of length l P ͞20.…”

Section: Materials and Methods Nsalexmentioning

confidence: 99%

Probing structural heterogeneities and fluctuations of nucleic acids and denatured proteins

Laurence

Kong²,

Jäger³

et al. 2005

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

226

230

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We study protein and nucleic acid structure and dynamics using single-molecule FRET and alternating-laser excitation. Freely diffusing molecules are sorted into subpopulations based on singlemolecule signals detected within 100 s to 1 ms. Distance distributions caused by fluctuations faster than 100 s are studied within these subpopulations by using time-correlated singlephoton counting. Measured distance distributions for dsDNA can be accounted for by considering fluorophore linkers and fluorophore rotational diffusion, except that we find smaller fluctuations for internally labeled dsDNA than DNA with one of the fluorophores positioned at a terminal site. We find that the electrostatic portion of the persistence length of short single-stranded poly(dT) varies approximately as the ionic strength (I) to the ؊1͞2 power (I ؊1/2 ), and that the average contribution to the contour length per base is 0.40 -0.45 nm. We study unfolded chymotrypsin inhibitor 2 (CI2) and unfolded acyl-CoA binding protein (ACBP) even under conditions where folded and unfolded subpopulations coexist (contributions from folded proteins are excluded by using alternating-laser excitation). At lower denaturant concentrations, unfolded CI2 and ACBP are more compact and display larger fluctuations than at higher denaturant concentrations where only unfolded proteins are present. The experimentally measured fluctuations are larger than the fluctuations predicted from a Gaussian chain model or a wormlike chain model. We propose that the larger fluctuations may indicate transient residual structure in the unfolded state.conformational dynamics ͉ protein folding ͉ single-molecule fluorescence spectroscopy ͉ nucleic acid structure ͉ fluorescence resonance energy transfer I n contrast to neutral homopolymers (1), biopolymers such as proteins and nucleic acids have long-range Coulomb interactions (2) and specific, intrachain interactions that strongly affect their structure and dynamics. Protein folding is the most spectacular manifestation of these interactions (3). Understanding biopolymer energy landscapes requires measurements of fluctuating distance distributions occurring over short distances (0.1-100 nm) and many time scales (picoseconds to minutes) (4). The structure and dynamics of charged polymer chains (polyelectrolytes), including dsDNA and ssDNA, are strongly affected by long-range, electrostatic repulsion (2). Because simulations and theory have focused on dilute, single-chain properties, a regime difficult to access by conventional methods, experimental validation of many predictions has been lacking (5). In protein folding studies, folded, unfolded, and partially folded species may be simultaneously present and rapidly interconverting, obscuring the properties of individual species. An experimental method that unravels distance distributions and fast conformational fluctuations is therefore much-needed.Previous protein folding studies with single-molecule FRET (6-8) measured distance distributions with time resolutions of Ϸ100 s. Using ...

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“…The radius of each bead in a 50-bead chain is set equal to the hydrodynamic radius of B-DNA. We use the value R HYD ϭ15.92 Å, 24 corresponding to approximately 4.68 3.4 Å basepair steps. Each bead then represents Ϸ9.36 bp.…”

Section: ͑5͒mentioning

confidence: 99%

Transcription-driven twin supercoiling of a DNA loop: A Brownian dynamics study

Mielke

Fink

Krishnan

et al. 2004

The Journal of Chemical Physics

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The torque generated by RNA polymerase as it tracks along double-stranded DNA can potentially induce long-range structural deformations integral to mechanisms of biological significance in both prokaryotes and eukaryotes. In this paper, we introduce a dynamic computer model for investigating this phenomenon. Duplex DNA is represented as a chain of hydrodynamic beads interacting through potentials of linearly elastic stretching, bending, and twisting, as well as excluded volume. The chain, linear when relaxed, is looped to form two open but topologically constrained subdomains. This permits the dynamic introduction of torsional stress via a centrally applied torque. We simulate by Brownian dynamics the 100 μs response of a 477-base pair B-DNA template to the localized torque generated by the prokaryotic transcription ensemble. Following a sharp rise at early times, the distributed twist assumes a nearly constant value in both subdomains, and a succession of supercoiling deformations occurs as superhelical stress is increasingly partitioned to writhe. The magnitude of writhe surpasses that of twist before also leveling off when the structure reaches mechanical equilibrium with the torsional load. Superhelicity is simultaneously right handed in one subdomain and left handed in the other, as predicted by the “transcription-induced twin-supercoiled-domain” model [L. F. Liu and J. C. Wang, Proc. Natl. Acad. Sci. U.S.A. 84, 7024 (1987)]. The properties of the chain at the onset of writhing agree well with predictions from theory, and the generated stress is ample for driving secondary structural transitions in physiological DNA.

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Monte Carlo approach to the analysis of the rotational diffusion of wormlike chains

Cited by 265 publications

References 40 publications

Cyclization of short DNA fragments and bending fluctuations of the double helix

Cyclization of short DNA fragments and bending fluctuations of the double helix

Probing structural heterogeneities and fluctuations of nucleic acids and denatured proteins

Transcription-driven twin supercoiling of a DNA loop: A Brownian dynamics study

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