58 research outputs found
Monte Carlo implementation of supercoiled double-stranded DNA
Metropolis Monte Carlo simulation is used to investigate the elasticity of
torsionally stressed double-stranded DNA, in which twist and supercoiling are
incorporated as a natural result of base-stacking interaction and backbone
bending constrained by hydrogen bonds formed between DNA complementary
nucleotide bases. Three evident regimes are found in extension versus torsion
and/or force versus extension plots: a low-force regime in which over- and
underwound molecules behave similarly under stretching; an intermediate-force
regime in which chirality appears for negatively and positively supercoiled DNA
and extension of underwound molecule is insensitive to the supercoiling degree
of the polymer; and a large-force regime in which plectonemic DNA is fully
converted to extended DNA and supercoiled DNA behaves quite like a torsionless
molecule. The striking coincidence between theoretic calculations and recent
experimental measurement of torsionally stretched DNA [Strick et al., Science
{\bf 271}, 1835 (1996), Biophys. J. {\bf 74}, 2016 (1998)] strongly suggests
that the interplay between base-stacking interaction and permanent
hydrogen-bond constraint takes an important role in understanding the novel
properties of elasticity of supercoiled DNA polymer.Comment: 21 pages, 6 PS figures. To appear at Biophys.
Theoretical models of DNA topology simplification by type IIA DNA topoisomerases
It was discovered 12 years ago that type IIA topoisomerases can simplify DNA topology—the steady-state fractions of knots and links created by the enzymes are many times lower than the corresponding equilibrium fractions. Though this property of the enzymes made clear biological sense, it was not clear how small enzymes could selectively change the topology of very large DNA molecules, since topology is a global property and cannot be determined by a local DNA–protein interaction. A few models, suggested to explain the phenomenon, are analyzed in this review. We also consider experimental data that both support and contravene these models
Torsional Directed Walks, Entropic Elasticity, and DNA Twist Stiffness
DNA and other biopolymers differ from classical polymers due to their
torsional stiffness. This property changes the statistical character of their
conformations under tension from a classical random walk to a problem we call
the `torsional directed walk'. Motivated by a recent experiment on single
lambda-DNA molecules [Strick et al., Science 271 (1996) 1835], we formulate the
torsional directed walk problem and solve it analytically in the appropriate
force regime. Our technique affords a direct physical determination of the
microscopic twist stiffness C and twist-stretch coupling D relevant for DNA
functionality. The theory quantitatively fits existing experimental data for
relative extension as a function of overtwist over a wide range of applied
force; fitting to the experimental data yields the numerical values C=120nm and
D=50nm. Future experiments will refine these values. We also predict that the
phenomenon of reduction of effective twist stiffness by bend fluctuations
should be testable in future single-molecule experiments, and we give its
analytic form.Comment: Plain TeX, harvmac, epsf; postscript available at
http://dept.physics.upenn.edu/~nelson/index.shtm
Modeling Bacterial DNA: Simulation of Self-avoiding Supercoiled Worm-Like Chains Including Structural Transitions of the Helix
Under supercoiling constraints, naked DNA, such as a large part of bacterial
DNA, folds into braided structures called plectonemes. The double-helix can
also undergo local structural transitions, leading to the formation of
denaturation bubbles and other alternative structures. Various polymer models
have been developed to capture these properties, with Monte-Carlo (MC)
approaches dedicated to the inference of thermodynamic properties. In this
chapter, we explain how to perform such Monte-Carlo simulations, following two
objectives. On one hand, we present the self-avoiding supercoiled Worm-Like
Chain (ssWLC) model, which is known to capture the folding properties of
supercoiled DNA, and provide a detailed explanation of a standard MC simulation
method. On the other hand, we explain how to extend this ssWLC model to include
structural transitions of the helix.Comment: Book chapter to appear in The Bacterial Nucleoid, Methods and
Protocols, Springer serie
Temperature dependence of DNA persistence length
We have determined the temperature dependence of DNA persistence length, a, using two different methods. The first approach was based on measuring the j-factors of short DNA fragments at various temperatures. Fitting the measured j-factors by the theoretical equation allowed us to obtain the values of a for temperatures between 5°C and 42°C. The second approach was based on measuring the equilibrium distribution of the linking number between the strands of circular DNA at different temperatures. The major contribution into the distribution variance comes from the fluctuations of DNA writhe in the nicked circular molecules which are specified by the value of a. The computation-based analysis of the measured variances was used to obtain the values of a for temperatures up to 60°C. We found a good agreement between the results obtained by these two methods. Our data show that DNA persistence length strongly depends on temperature and accounting for this dependence is important in quantitative comparison between experimental results obtained at different temperatures
Kinking the double helix by bending deformation
DNA bending and torsional deformations that often occur during its functioning inside the cell can cause local disruptions of the regular helical structure. The disruptions created by negative torsional stress have been studied in detail, but those caused by bending stress have only been analyzed theoretically. By probing the structure of very small DNA circles, we determined that bending stress disrupts the regular helical structure when the radius of DNA curvature is smaller than 3.5 nm. First, we developed an efficient method to obtain covalently closed DNA minicircles. To detect structural disruptions in the minicircles we treated them by single-strand-specific endonucleases. The data showed that the regular DNA structure is disrupted by bending deformation in the 64–65-bp minicircles, but not in the 85–86-bp minicircles. Our results suggest that strong DNA bending initiates kink formation while preserving base pairing
Critical exponents for random knots
The size of a zero thickness (no excluded volume) polymer ring is shown to
scale with chain length in the same way as the size of the excluded volume
(self-avoiding) linear polymer, as , where . The
consequences of that fact are examined, including sizes of trivial and
non-trivial knots.Comment: 4 pages, 0 figure
Conformational dynamics and internal friction in homopolymer globules: equilibrium vs. non-equilibrium simulations
We study the conformational dynamics within homopolymer globules by solvent-implicit Brownian dynamics simulations. A strong dependence of the internal chain dynamics on the Lennard-Jones cohesion strength ε and the globule size N [subscript G] is observed. We find two distinct dynamical regimes: a liquid-like regime (for ε ε[subscript s] with slow internal dynamics. The cohesion strength ε[subscript s] of this freezing transition depends on N G . Equilibrium simulations, where we investigate the diffusional chain dynamics within the globule, are compared with non-equilibrium simulations, where we unfold the globule by pulling the chain ends with prescribed velocity (encompassing low enough velocities so that the linear-response, viscous regime is reached). From both simulation protocols we derive the internal viscosity within the globule. In the liquid-like regime the internal friction increases continuously with ε and scales extensive in N [subscript G] . This suggests an internal friction scenario where the entire chain (or an extensive fraction thereof) takes part in conformational reorganization of the globular structure.American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowshi
Biophysics of DNA
Surveying the last sixty years of research, this book describes the physical properties of DNA in the context of its biological functioning. It is designed to enable both students and researchers of molecular biology, biochemistry and physics to better understand the biophysics of DNA, addressing key questions and facilitating further research. The chapters integrate theoretical and experimental approaches, emphasising throughout the importance of a quantitative knowledge of physical properties in building and analysing models of DNA functioning. For example, the book shows how the relationship between DNA mechanical properties and the sequence specificity of DNA-protein binding can be analyzed quantitatively by using our current knowledge of the physical and structural properties of DNA. Theoretical models and experimental methods in the field are critically considered to enable the reader to engage effectively with the current scientific literature on the physical properties of DNA
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