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  • 1
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 92 (1990), S. 6294-6305 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: This paper develops accurate and computationally tractable, theoretical methods to analyze equilibrium heteropolymeric transitions in superhelical DNAs of specified sequence and kilo-base length. Although these methods are generally applicable, their development here is focused primarily on superhelical strand separation, a heteropolymeric transition of great biological importance to which every base pair in a duplex DNA molecule is susceptible. Because the total number of states of this transition grows exponentially with molecular length, exact analytic methods that consider all possible states are not feasible for DNAs of practical interest. First, an approximate statistical mechanical analysis is developed in which all states are considered whose free energies do not exceed that of the minimum energy state by more than a specified threshold amount. An approximate partition function is constructed using these states, from which estimates of the equilibrium values of important transition parameters are calculated. Next, a density of states analysis is performed to estimate the influence of the neglected, high energy states. Its results are used to refine the computed equilibrium parameter values, correcting for the effects of the neglected states. Only the transition profile (the probability of transition of each base pair in the sequence) cannot be refined in this manner, although its overall accuracy can be assessed. Sample calculations analyzing the strand separation transition in superhelical pBR322 DNA show that the analytic methods developed here yield accurate results in a computationally feasible manner. Moreover, the predictions of this analysis agree closely with experimental results.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 175-203 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Because the level of DNA superhelicity varies with the cellular energy charge, it can change rapidly in response to a wide variety of altered nutritional and environmental conditions. This is a global alteration, affecting the entire chromosome and the expression levels of all operons whose promoters are sensitive to superhelicity. In this way, the global pattern of gene expression may be dynamically tuned to changing needs of the cell under a wide variety of circumstances. In this article, we propose a model in which chromosomal superhelicity serves as a global regulator of gene expression in Escherichia coli, tuning expression patterns across multiple operons, regulons, and stimulons to suit the growth state of the cell. This model is illustrated by the DNA supercoiling-dependent mechanisms that coordinate basal expression levels of operons of the ilv regulon both with one another and with cellular growth conditions.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 103 (1995), S. 8653-8665 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Metropolis–Monte Carlo algorithms are developed to analyze the strand separation transition in circular superhelical DNA molecules. Moves that randomize the locations of unpaired regions are required in order to diminish correlations among the sampled states. This approach enables accurate simulations to be performed in reasonable computational times. Sufficient conditions to guarantee the formal correctness of the complete algorithm are proven to hold. The computation time required scales at most quadratically with molecular length, and is approximately independent of linking difference. Techniques are developed to estimate the sample size and other calculation parameters needed to achieve a specified accuracy. When the results of Monte Carlo calculations that use shuffling operations are compared with those from statistical mechanical calculations, excellent agreement is found. The Monte Carlo methodology makes possible calculations of transition behavior in cases where alternative approaches are intractable, such as in long molecules under circumstances where several runs of open base pairs occur simultaneously. It also allows the analysis of transitions in cases where the base pair separation energies vary in complex manners, such as through near-neighbor interactions, or the presence of modified bases, abasic sites, or bound molecules. © 1995 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 21-53 
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: We review the history of DNA mechanics and its analysis. We evaluate several methods to analyze the structures of superhelical DNA molecules, each predicated on the assumption that DNA can be modeled with reasonable accuracy as an extended, linearly elastic polymer. Three main approaches are considered: mechanical equilibrium methods, which seek to compute minimum energy conformations of topologically constrained molecules; statistical mechanical methods, which seek to compute the Boltzmann distribution of equilibrium conformations that arise in a finite temperature environment; and dynamic methods, which seek to compute deterministic trajectories of the helix axis by solving equations of motion. When these methods include forces of self-contact, which prevent strand passage and preserve the topological constraint, each predicts plectonemically interwound structures. On the other hand, the extent to which these mechanical methods reliably predict energetic and thermodynamic properties of superhelical molecules is limited, in part because of their inability to account explicitly for interactions involving solvent. Monte Carlo methods predict the entropy associated with supercoiling to be negative, in conflict with a body of experimental evidence that finds it is large and positive, as would be the case if superhelical deformations significantly disrupt the ordering of ambient solvent molecules. This suggests that the large-scale conformational properties predicted by elastomechanical models are not the only ones determining the energetics and thermodynamics of supercoiling. Moreover, because all such models that preserve the topological constraint correctly predict plectonemic interwinding, despite these and other limitations, this constraint evidently dominates energetic and thermodynamic factors in determining supercoil geometry. Therefore, agreement between predicted structures and structures obtained experimentally, for example, by electron microscopy, does not in itself provide evidence for the correctness or completeness of any given model of DNA mechanics.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The leuV operon of Escherichia coli encodes three of the four genes for the tRNA1Leu isoacceptors. Transcription from this and other stable RNA promoters is known to be affected by a cis-acting UP element and by Fis protein interactions with the carboxyl-terminal domain of the α-subunits of RNA polymerase. In this report, we suggest that transcription from the leuV promoter also is activated by a Fis-mediated, DNA supercoiling-dependent mechanism similar to the IHF-mediated mechanism described previously for the ilvPG promoter (S. D. Sheridan et al., 1998, J Biol Chem 273: 21298–21308). We present evidence that Fis binding results in the translocation of superhelical energy from the promoter-distal portion of a supercoiling-induced DNA duplex destabilized (SIDD) region to the promoter-proximal portion of the leuV promoter that is unwound within the open complex. A mutant Fis protein, which is defective in contacting the carboxyl-terminal domain of the α-subunits of RNA polymerase, remains competent for stimulating open complex formation, suggesting that this DNA supercoiling-dependent component of Fis-mediated activation occurs in the absence of specific protein interactions between Fis and RNA polymerase. Fis-mediated translocation of superhelical energy from upstream binding sites to the promoter region may be a general feature of Fis-mediated activation of transcription at stable RNA promoters, which often contain A+T-rich upstream sequences.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 286 (1980), S. 637-638 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Consider a linear segment containing N base pairs, of which NZ sequential pairs may undergo the B-Z transition. Let this segment be twisted by q turns away from its unstressed (hence totally B-form) shape. This torsional deformation will be partitioned between local transitions to the Z-form and ...
    Type of Medium: Electronic Resource
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  • 7
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    Baltimore, Md. : Periodicals Archive Online (PAO)
    Behavioral science. 23:5 (1978:Sept.) 355 
    ISSN: 0005-7940
    Topics: Psychology
    Notes: APPLICATIONS OF CATASTROPHE THEORY IN THE BEHAVIORAL AND LIFE SCIENCES
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  • 8
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 18 (1979), S. 609-623 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A general model for the large-scale, time-independent structure of duplex DNA is developed based on elastic considerations. The general conditions of elastic equilibrium are given. These equations are solved for the equilibrium shape of stressed duplex DNA, based on the assumption that the double helix behaves mechanically as a symmetric, linearly elastic rod. It is shown that, in general, two orders of superhelicity will arise at equilibrium. Several possible applications of this approach to the supercoiling of closed circular DNA are described.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 19 (1980), S. 2143-2164 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The theoretical kinetics are analyzed for reactions between torsionally stressed DNA and another compound which reacts at different rates with portions of the substrate molecule which are in different conformational states. These reactions are assumed to obey Michaelis-Menten kinetics, so no cooperative effects occur. The DNA is regarded as being susceptible to a stress-induced local conformational transition as described recently by Benham. Briefly, alterations in torsional stress consequent on superhelicity effectively change the relative concentrations of the two conformational states of the substrate, thereby influencing the course of the reaction. This theory is developed for transition between the B-form helix and the single-stranded, random-coil states. To illustrate the influence of posited stress-induced melting on kinetics, calculations are made on simple models of two biochemical phenomena. First, the variations in initial nicking rates of single-strand-specific endonucleases with substrate superhelicity are interpreted as arising from changes in the concentration of (stress-induced) single-stranded binding sites. Second, the observed dependence of the transcription rate of RNA polymerase core enzyme on substrate superhelicity is interpreted in terms of a model in which the rate-limiting step in the initiation event is the formation of a complex between the enzyme and a single-stranded region. Related experimental results are shown to be qualitatively consistent with the suggestion that sufficiently supercoiled DNA contains locally melted regions.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2477-2495 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This paper analyzes the elastic equilibrium conformations of duplex DNA constrained by the constancy of its molecular linking number, Lk. The DNA is regarded as having the mechanical properties of a homogeneous, linearly elastic substance with symmetric cross section. Integral representations of the writhing number Wr and of Lk are developed, in terms of which the equilibria are given as solutions to an isoperimetric problem. It is shown that the Euler angles defining equilibrium conformations must obey equations identical to those governing unconstrained equilibria. A scaling law is developed stating that molecules supercoiled the same amount ΔLk will have geometrically similar elastic equilibria regardless of their length. Thus, comparisons among molecules of properties related to their large-scale tertiary structure should be referred to differences in ΔLk rather than to their superhelix densities. Specific conditions on the elastic equilibrium conformations are developed that are necessary for ring closure. The equilibrium superhelical conformations accessible to closed-ring molecules are shown to approximate toroidal helices. Questions relating to the stability and nonuniqueness of equilibria are treated briefly. A comparison is made between these toroidal conformations and interwound configurations, which are shown to be stable, although they are not equilibria in the present sense. It is suggested that entropic factors are responsible for favouring the toroidal conformation in solution.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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