Inducing and modulating anisotropic DNA bends by pseudocomplementary peptide nucleic acids

DNA bending is significant for various DNA functions in the cell. Here, we demonstrate that pseudocomplementary peptide nucleic acids (pcPNAs) represent a class of versatile, sequence-specific DNA-bending agents. The occurrence of anisotropic DNA bends induced by pcPNAs is shown by gel electrophoretic phasing analysis. The magnitude of DNA bending is determined by circular permutation assay and by electron microscopy, with good agreement of calculated mean values between both methods. Binding of a pair of 10-meric pcPNAs to its target DNA sequence results in moderate DNA bending with a mean value of 40–45°, while binding of one self-pc 8-mer PNA to target DNA yields a somewhat larger average value of the induced DNA bend. Both bends are found to be in phase when the pcPNA target sites are separated by distances of half-integer numbers of helical turns of regular duplex DNA, resulting in an enhanced DNA bend with an average value in the range of 80–90°. The occurrence of such a sharp bend within the DNA double helix is confirmed and exploited through efficient formation of 170-bp-long DNA minicircles by means of dimerization of two bent DNA fragments. The pcPNAs offer two main advantages over previously designed classes of nonnatural DNAbending agents: they have very mild sequence limitations while targeting duplex DNA and they can easily be designed for a chosen target sequence, because their binding obeys the principle of complementarity. We conclude that pcPNAs are promising tools for inducing bends in DNA at virtually any chosen site

Chemical probing of the homopurine·homopyrimidine tract in supercoiled DNA at single-nucleotide resolution

AbstractLocal structure of the homopurine·homopyrimidine tract in a supercoiled plasmid pEJ4 was studied using chemical probes at single-nucleotide resolution. The conformation of the homopyrimidine strand was probed by osmium tetroxide, pyridine (Os,py) while that of the homopurine strand was tested by diethyl pyrocarbonate (DEPC), i.e. by probes reacting preferentially with single-stranded DNA. At weakly acidic pH values, a strong Os,py attack on three nucleotides at the centre of the (dC-dT)16 block and a weaker attack on two nucleotides at the end of the block were observed. DEPC modified adenines in the 5′-half of the homopurine strand. Os,py modification at the centre of the block corresponded to the loop of the hairpin formed by the homopyrimidine tract, while DEPC modification corresponded to the unstructured half of the homopurine strand in the model of protonated triplex H form of DNA

Long-range coupling and scalable architecture for superconducting flux qubits

Constructing a fault-tolerant quantum computer is a daunting task. Given any design, it is possible to determine the maximum error rate of each type of component that can be tolerated while still permitting arbitrarily large-scale quantum computation. It is an underappreciated fact that including an appropriately designed mechanism enabling long-range qubit coupling or transport substantially increases the maximum tolerable error rates of all components. With this thought in mind, we take the superconducting flux qubit coupling mechanism described in PRB 70, 140501 (2004) and extend it to allow approximately 500 MHz coupling of square flux qubits, 50 um a side, at a distance of up to several mm. This mechanism is then used as the basis of two scalable architectures for flux qubits taking into account crosstalk and fault-tolerant considerations such as permitting a universal set of logical gates, parallelism, measurement and initialization, and data mobility.Comment: 8 pages, 11 figure

Master equation approach to DNA-breathing in heteropolymer DNA

After crossing an initial barrier to break the first base-pair (bp) in double-stranded DNA, the disruption of further bps is characterized by free energies between less than one to a few kT. This causes the opening of intermittent single-stranded bubbles. Their unzipping and zipping dynamics can be monitored by single molecule fluorescence or NMR methods. We here establish a dynamic description of this DNA-breathing in a heteropolymer DNA in terms of a master equation that governs the time evolution of the joint probability distribution for the bubble size and position along the sequence. The transfer coefficients are based on the Poland-Scheraga free energy model. We derive the autocorrelation function for the bubble dynamics and the associated relaxation time spectrum. In particular, we show how one can obtain the probability densities of individual bubble lifetimes and of the waiting times between successive bubble events from the master equation. A comparison to results of a stochastic Gillespie simulation shows excellent agreement.Comment: 12 pages, 8 figure

DNA uptake into nuclei: Numerical and analytical results

The dynamics of polymer translocation through a pore has been the subject of recent theoretical and experimental works. We have considered theoretical estimates and performed computer simulations to understand the mechanism of DNA uptake into the cell nucleus, a phenomenon experimentally investigated by attaching a small bead to the free end of the double helix and pulling this bead with the help of an optical trap. The experiments show that the uptake is monotonous and slows down when the remaining DNA segment becomes very short. Numerical and analytical studies of the entropic repulsion between the DNA filament and the membrane wall suggest a new interpretation of the experimental observations. Our results indicate that the repulsion monotonically decreases as the uptake progresses. Thus, the DNA is pulled in (i) either by a small force of unknown origin, and then the slowing down can be interpreted only statistically; (ii) or by a strong but slow ratchet mechanism, which would naturally explain the observed monotonicity, but then the slowing down requires additional explanations. Only further experiments can unambiguously distinguish between these two mechanisms.Comment: 12 pages, 6 figures, submitted to J. Phys. Cond. Ma

Gauge vortex dynamics at finite mass of bosonic fields

The simple derivation of the string equation of motion adopted in the nonrelativistic case is presented, paying the special attention to the effects of finite masses of bosonic fields of an Abelian Higgs model. The role of the finite mass effects in the evaluation of various topological characteristics of the closed strings is discussed. The rate of the dissipationless helicity change is calculated. It is demonstrated how the conservation of the sum of the twisting and writhing numbers of the string is recovered despite the changing helicity.Comment: considerably revised to include errata to journal versio

On topological interpretation of quantum numbers

It is shown how one can define vector topological charges for topological exitations of non-linear sigma-models on compact homogeneous spaces T_G and G/T_G (where G is a simple compact Lie group and T_G is its maximal commutative subgroup). Explicit solutions for some cases, their energies and interaction of different topological charges are found. A possibility of the topological interpretation of the quantum numbers of groups and particles is discussed.Comment: 20 pages, Latex 2e, modified versio

Ribbon polymers in poor solvents: layering transitions in annular and tubular condensates

We study the structures of a ribbon or ladder polymer immersed in poor solvents. The anisotropic bending rigidity coupled with the surface tension leads ribbon polymers to spontaneous formation of highly anisotropic condensates in poor solvents. Unlike ordinary flexible polymers these condensates undergo a number of distinct layering transitions as a function of chain length or solvent quality, and the size of condensates becomes non-monotonic function of chain length. We show that the fluctuations of the condensates are in general small and these condensates are stable.Comment: 5 pages, 5 figures, visulaize missing figure number

Thermodynamics and Topology of Disordered Systems: Statistics of the Random Knot Diagrams on Finite Lattice

The statistical properties of random lattice knots, the topology of which is determined by the algebraic topological Jones-Kauffman invariants was studied by analytical and numerical methods. The Kauffman polynomial invariant of a random knot diagram was represented by a partition function of the Potts model with a random configuration of ferro- and antiferromagnetic bonds, which allowed the probability distribution of the random dense knots on a flat square lattice over topological classes to be studied. A topological class is characterized by the highest power of the Kauffman polynomial invariant and interpreted as the free energy of a q-component Potts spin system for q->infinity. It is shown that the highest power of the Kauffman invariant is correlated with the minimum energy of the corresponding Potts spin system. The probability of the lattice knot distribution over topological classes was studied by the method of transfer matrices, depending on the type of local junctions and the size of the flat knot diagram. The obtained results are compared to the probability distribution of the minimum energy of a Potts system with random ferro- and antiferromagnetic bonds.Comment: 37 pages, latex-revtex (new version: misprints removed, references added