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DNA cyclization is a powerful technique to gain insight into the nature of DNA bending. While the worm-like chain model provides a good description of small to moderate bending fluctuations, it is expected to break down for large bending. Recent cyclization experiments on strongly-bent shorter molecules indeed suggest enhanced flexibility over and above that expected from the worm-like chain. Here, we use a coarse-grained model of DNA to investigate the subtle thermodynamics of DNA cyclization for molecules ranging from 30 to 210 base pairs. As the molecules get shorter we find increasing deviations between our computed equilibrium j-factor and the classic worm-like chain predictions of Shimada and Yamakawa for a torsionally aligned looped molecule. These deviations are due to sharp kinking, first at nicks, and only subsequently in the body of the duplex. At the shortest lengths, substantial fraying at the ends of duplex domains is the dominant method of relaxation. We also estimate the dynamic j-factor measured in recent FRET experiments. We find that the dynamic j-factor is systematically larger than its equilibrium counterpart - with the deviation larger for shorter molecules - because not all the stress present in the fully cyclized state is present in the transition state. These observations are important for the interpretation of recent cyclization experiments, suggesting that measured anomalously high j-factors may not necessarily indicate non-WLC behavior in the body of duplexes.

The determination of the double helical structure of DNA in 1953 remains the landmark event in the development of modern biological and biomedical science. This structure has also been the starting point for the determination of some 2000 DNA crystal structures in the subsequent 68 years. Their structural diversity has extended to the demonstration of sequence-dependent local structure in duplex DNA, to DNA bending in short and long sequences and in the DNA wound round the nucleosome, and to left-handed duplex DNAs. Beyond the double helix itself, in circumstances where DNA sequences are or can be induced to unwind from being duplex, a wide variety of topologies and forms can exist. Quadruplex structures, based on four-stranded cores of stacked G-quartets, are prevalent though not randomly distributed in the human and other genomes and can play roles in transcription, translation, and replication. Yet more complex folds can result in DNAs with extended tertiary structures and enzymatic/catalytic activity. The Protein Data Bank is the depository of all these structures, and the resource where structures can be critically examined and validated, as well as compared one with another to facilitate analysis of conformational and base morphology features. This review will briefly survey the major structural classes of DNAs and illustrate their significance, together with some examples of how the use of the Protein Data Bank by for example, data mining, has illuminated DNA structural concepts.

Ethanol precipitation process for purification of branched dextrin (BD) in Nageli amylodextrin from waxy rice starch was developed. Temperature and ethanol concentration for precipitation were main parameters affecting the recovery and purity of BD, and the purification condition at 4 °C and 10 % (v/v) ethanol in water was adopted. After four-time precipitation, the BD recovery was 34.6 %, whereas the purity improved from 78.5 % at the initial to 94.5 % at the four-time purified BD (BD4). BD4 mainly showed a chain length distribution between 18 to 35 with a mode length of 25, which shifted after enzymatic debranching with isoamylase to that between 9 and 20 with a mode length of 14. Each purified BD was solubilized in water, and each solution was mixed with methanol-water at 25 °C to a final methanol concentration of 16 M. The flakes of BD precipitated with 16 M methanol exhibited an A-type crystal structure by an X-ray diffraction analysis, and the speed generation of white flakes in 16 M methanol dramatically increased as the purification time increased. The effect of addition of highly branched cyclic dextrin (HBCD) or sodium tetraborate on BD aggregation in 16 M methanol was also investigated, where the former retarded aggregation but the latter had no effect on the velocity. Thus, the purified BD enables rapid characterization of aggregation of double helix structures of A-type crystal structure, and screening of compounds which could affect the phenomena for prediction of potentials in starch modification as well.

Evolution can increase the complexity of matter by self-organization into helical architectures, the best example being the DNA double helix. One common aspect, apparently shared by most of these architectures, is the presence of covalent bonds within the helix backbone. Here, we report the unprecedented crystal structures of a metal complex that self-organizes into a continuous double helical structure, assembled by non-covalent building blocks. Built up solely by weak stacking interactions, this alternating tread stairs-like double helical assembly mimics the DNA double helix structure. Starting from a racemic mixture in aqueous solution, the ruthenium(II) polypyridyl complex forms two polymorphic structures of a left-handed double helical assembly of only the Λ-enantiomer. The stacking of the helices is different in both polymorphs: a crossed woodpile structure versus a parallel columnar stacking. ispartof: Angewandte Chemie - International Edition vol:53 issue:34 pages:8959-8962 ispartof: location:Germany status: published

International audience; An aromatic oligoamide sequence was designed to fold and self-assemble into a double helical host having a cylindrical cavity complementary to linear oligo–carbamates guests. Formation of helical pseudo–rotaxane complexes – foldaxanes – between the host and guests having binding stations of different affinities was evidenced by NMR and x-ray crystallography. Rod-like guests possessing two or three binding stations, long alkyl or oligoethylene glycol spacers or bulky barriers in-between the binding stations, and a single bulky stopper at one end, were synthesized. Kinetic investigations of the threading and translation of the double helix along multistation rods were monitored by 1 H NMR. Results show that multiple events may occur upon sliding of the host from the non-bulky end of the rod to reach the thermodynamically most stable state before unfolding-mediated dissociation has time to take place, including binding on intermediate stations and rapid sliding along non-binding spacers. Conversely, installing a kinetic barrier that blocks sliding allows for the deliberate integration of a helix dissociation re-association step in the supramolecular trajectory. Typical sliding processes can be monitored over the course of hours whereas steps involving unwinding/rewinding of the helix proceeded over the course of days. These results further demonstrate the interest of foldaxanes to design complex sequences of supramolecular events within networks of equilibria through the adjustment of the kinetics of the individual steps involved.

Recent measurements of the distribution of end-to-end distance in short DNA molecules infer cooperative stretching fluctuations. The assumptions underlying the analysis can be questioned if transient, thermally induced defects producing a localized decrease in bending stiffness are present in thermal equilibrium, such as regions in which DNA melts locally (bubbles), sustains large-angle bends (kinks), or can locally transform into an alternative (S-DNA) state. We study a generalized discrete worm-like chain model for DNA, capable of describing these experiments, showing that the model yields accurate fits to available experimental data. Our results indicate that DNA bending arising from such localized defects, rather than solely stretching, can be an equal contributor to end-to-end distance fluctuations for 35-bp DNA and contributes nontrivially to such fluctuations at all scales below the persistence length. The analysis suggests that such fluctuations should exhibit a scale-dependent cooperativity, specifically relevant in determining the behavior of short chains, but which saturates rapidly to a length-independent value for longer DNA, to ensure a consistent physical description of DNA across multiple scales. Our approach provides a minimal, yet accurate, coarse-grained description of DNA at the subpersistence length scales of current experimental interest.

The biological importance of nucleic acids for the storage, expression and regulation of genetic information is now well understood. By taming the chemical synthesis of these biomolecules, chemists have been able to engineer new architectures based on the ability of DNA and RNA to fold into secondary or even more complex tertiary structures with applications in medicinal chemistry, diagnostics or even material sciences. Exploiting the fascinating helical structure of DNA and RNA to develop new chiral bio-hybrid catalysts capable of promoting highly stereoselective transformations under mild and eco-compatible conditions is also an emerging area of research. In this short review, we report our recent results in the field of DNA-based asymmetric catalysis as well as the challenges and promising perspectives that lie in front of us.

Em The double helix, James Watson narra sua versão da construção do modelo da dupla hélice do DNA, na qual indica que Rosalind Franklin, física especialista em cristalografia de raios X, desenvolveu trabalhos empíricos fundamentais para a construção do modelo de Watson e Crick. O relato de Watson dá origem a um problema historiográfico: por que Franklin, que dispunha dos dados empíricos produzidos por ela mesma, não decifrou a estrutura molecular do DNA? O próprio Watson fornece uma resposta, ao sugerir que Franklin não teria nenhuma inclinação teórica para a representação helicoidal do DNA, fazendo trabalho estritamente experimental. Essa sugestão tem recebido réplicas de historiadores, de modo que o problema historiográfico subentendido no relato de Watson se manteve até hoje. No entanto, é possível obter pistas de que, antes de estar envolvida com a construção de uma estrutura para o DNA, Franklin estava preocupada em mapear todos os aspectos da molécula. Este artigo tem dois objetivos: mostrar que a linha de defesa de Franklin adotada por alguns de seus defensores muitas vezes acaba, na verdade, por comprometê-la e apresentar um esboço de interpretação alternativa que, ao não atribuir a Franklin o objetivo principal de construção da estrutura molecular para o DNA, acaba por dar-lhe um papel muito mais confortável do ponto de vista histórico (o que não significará negar que ela tivesse o objetivo secundário de alcançar uma estrutura para o DNA). In The double helix, James Watson narrated his version of the building of the DNA double-helix model, in which he indicates that Rosalind Franklin, a physicist specialized in X-Ray crystallography, developed empirical fundamental works to Watson and Crick's model construction. Watson's report gave rise to a historiographical problem: why Franklin, who disposes of the empirical data produced by herself, did not decipher the DNA molecular structure? Watson himself provides an answer, suggesting that Franklin had no theoretical inclination for a helicoidal representation of DNA, making strictly experimental work. This suggestion has received replies by historians, so that the historiographical problem subjacent to Watson's report maintains its actuality. Nevertheless, it is possible to obtain clues that, rather getting involved in the building of a new structure for DNA, Franklin was concerned with mapping all the aspects of the molecule. This article has two aims: showing that Franklin's line of defense adopted by some of her defenders in fact occasionally end up compromising Franklin, and presenting an outline of an alternative interpretation which, not attributing to Franklin the main goal of building a molecular structure for DNA, ends up giving her a much more comfortable role according to the historical point of view (which does not mean denying that she had the secondary goal of reaching a structure for DNA).

The year 2016 marks the centenary of the birth of Francis Crick (1916–2004), who made outstanding contributions to genetics and neuroscience. In 1953, in a collaborative study, Francis Crick and James Watson discovered the DNA double helix, and in 1962 they and Maurice Wilkins were awarded the Noble Prize in Physiology or Medicine. Crick subsequently became very interested in neuroscience, particularly consciousness and its relationship to the claustrum, a small gray matter structure between the insula and putamen. RESUMO O ano de 2016 é o centenário de nascimento de Francis Crick (1916–2004), físico, biólogo e neurocientista, cujas contribuições para a genética e a neurociência foram magníficas. Crick, em um estudo colaborativo com Watson, descobriu a estrutura molecular do DNA (dupla hélice) em 1953, e em 1962 ambos receberam o prêmio Nobel de Fisiologia ou Medicina, junto com Wilkins. Após Crick tornou-se muito interessado na área de neurociência, particularmente no estudo da consciência, e a sua relação com o claustrum, uma pequena estrutura de substância cinzenta localizada entre a ínsula e o putame.

The rupture of double-stranded DNA under stress is a key process in biophysics and nanotechnology. In this article, we consider the shear-induced rupture of short DNA duplexes, a system that has been given new importance by recently designed force sensors and nanotechnological devices. We argue that rupture must be understood as an activated process, where the duplex state is metastable and the strands will separate in a finite time that depends on the duplex length and the force applied. Thus, the critical shearing force required to rupture a duplex depends strongly on the time scale of observation. We use simple models of DNA to show that this approach naturally captures the observed dependence of the force required to rupture a duplex within a given time on duplex length. In particular, this critical force is zero for the shortest duplexes, before rising sharply and then plateauing in the long length limit. The prevailing approach, based on identifying when the presence of each additional base pair within the duplex is thermodynamically unfavorable rather than allowing for metastability, does not predict a time-scale-dependent critical force and does not naturally incorporate a critical force of zero for the shortest duplexes. We demonstrate that our findings have important consequences for the behavior of a new force-sensing nanodevice, which operates in a mixed mode that interpolates between shearing and unzipping. At a fixed time scale and duplex length, the critical force exhibits a sigmoidal dependence on the fraction of the duplex that is subject to shearing.

Cataloged from PDF version of article. Carbon fiber reinforced polymers (CFRP) have emerged as the material of choice to satisfy increasing demand for lighter aircrafts. Machinability characteristics of CFRPs are quite different than those of metals; therefore, special tool designs have been developed for CFRP machining. The double helix end mill design compresses the upper and lower sides of the laminate using opposite helix angles that eliminate delamination. A mechanistic force model for double helix tools is developed based on milling force data obtained on flat end mills. The proposed model can be used to improve double helix tool designs and to optimize milling process parameters. 2013 CIRP.

The statistical mechanics of DNA denaturation under fixed linking number is qualitatively different from that of unconstrained DNA. Quantitatively different melting scenarios are reached from two alternative assumptions, namely, that the denatured loops are formed at the expense of (i) overtwist or (ii) supercoils. Recent work has shown that the supercoiling mechanism results in a picture similar to Bose-Einstein condensation where a macroscopic loop appears at T-c and grows steadily with temperature, while the nature of the denatured phase for the overtwisting case has not been studied. By extending an earlier result, we show here that a macroscopic loop appears in the overtwisting scenario as well. We calculate its size as a function of temperature and show that the fraction of the total sum of microscopic loops decreases above T-c, with a cusp at the critical point., Scientific and Technological Research Council of Turkey (TÜBİTAK); Israeli Science Foundation

12 páginas, 8 figuras -- PAGS nros. 3845-3853, The discrete regulation of supercoiling, catenation and knotting by DNA topoisomerases is well documented both in vivo and in vitro, but the interplay between them is still poorly understood. Here we studied DNA catenanes of bacterial plasmids arising as a result of DNA replication in Escherichia coli cells whose topoisomerase IV activity was inhibited. We combined high-resolution two-dimensional agarose gel electrophoresis with numerical simulations in order to better understand the relationship between the negative supercoiling of DNA generated by DNA gyrase and the DNA interlinking resulting from replication of circular DNA molecules. We showed that in those replication intermediates formed in vivo, catenation and negative supercoiling compete with each other. In interlinked molecules with high catenation numbers negative supercoiling is greatly limited. However, when interlinking decreases, as required for the segregation of newly replicated sister duplexes, their negative supercoiling increases. This observation indicates that negative supercoiling plays an active role during progressive decatenation of newly replicated DNA molecules in vivo., Spanish Ministerio de Ciencia e Innovacion[BIO2005-02224, BFU2008-00408/BMC, BFU2007-62670]; Swiss National Science Foundation[3100A0-116275]

The fundamental intramolecular frequency of a globular protein can be obtained from the measurements of acoustic velocities of bulk protein matter. This lowest frequency for common size molecules is shown to be above several hundred GHz. All modes below this frequency would then be intermolecular modes or bulk modes of the molecule and surrounding matter or tissue. The lowest frequency modes of an extended DNA double helix are also shown to be bulk modes because of interaction with water. Only DNA modes, whose frequency is well above 4 GHz, can be intrahelical modes, that is, confined to the helix rather than in the helix plus surroundings. Near 4 GHz, they are heavily damped and, therefore, not able to resonantly absorb. Modes that absorb radio frequency (RF) below this frequency are bulk modes of the supporting matter. Bulk modes rapidly thermalize all absorbed energy. The implication of these findings for the possibility of athermal RF effects is considered. The applicability of these findings for other biological molecules is discussed. (C) 2004 Wiley-Liss, Inc.

Interaction of water-soluble cationic copper(II) 5, 10, 15, 20-tetrakis[4-(N-methylpyridyl)] porphyrin (Cu(TMpy-P4)) with DNA attracts considerable attention and has been studied by a variety of techniques [1–3]. Cu(TMpy-P4) is known as a good intercalator into B-form DNA; the results of numerous studies [1–3] are consistent with copper porphyrin intercalation between consecutive GC base pairs or next to a GC base pair. However, porphyrin groove-binding at AT-rich regions of DNA also remains a possibility [3]. In cw Raman spectra, Cu(TMpy-P4) mixed with nucleic acids exhibit porphyrin core vibrations near 1570 (V2) and 1368 (V4) cm-1 , but under pulsed, high power excitation extra bands appear at 1550 (v2*) and 1346 (V4*) cm-1, which originate from a transient exciplex which can be formed at AT sites of the double helix [4–6]. These facts were discussed in [5] and, since Cu(TMpy-P4) is usually considered as preferentially intercalated, the mechanism of fast porphyrin translocation from GC to AT site has been proposed on the basis of nanosecond RR data [5].

In early May 1950, Bern chemistry professor Rudolf Signer traveled to a meeting of the Faraday Society in London with a few grams of DNA to report on his success in the isolation of nucleic acids from calf thymus glands. After the meeting, he distributed his DNA samples to interested parties amongst those present. One of the recipients was Maurice Wilkins, who worked intensively with nucleic acids at King's College in London. The outstanding quality of Signer's DNA – unique at that time – enabled Maurice Wilkins' colleague Rosalind Franklin to make the famous X-ray fiber diagrams that were a decisive pre-requisite for the discovery of the DNA double helix by James Watson and Francis Crick in the year 1953. Rudolf Signer, however, had already measured the physical characteristics of native DNA in the late thirties. In an oft-quoted work which he published in Nature in 1938, he described the thymonucleic acid as a long, thread-like molecule with a molecular weight of 500,000 to 1,000,000, in which the base rings lie in planes perpendicular to the long axis of the molecule. Signer's achievements and contributions to DNA research have, however, been forgotten even in Switzerland.

The conformation of the 1:1 complex of [Val 1 ] gramicidin A with caesium cations has been determined in methanol/chloroform (1:1) solution by 2-dimensional 1 H-NMR spectroscopy. The molecular structure was found to be a right-handed antiparallel double helical dimer ↑↓ππ L D 7.2 with 7.2 residues per turn, which incorporates two caesium cations.

We use cryo-electron microscopy (cryo-EM) to study the 3D shapes of 94-bp-long DNA minicircles and address the question of whether cyclization of such short DNA molecules necessitates the formation of sharp, localized kinks in DNA or whether the necessary bending can be redistributed and accomplished within the limits of the elastic, standard model of DNA flexibility. By comparing the shapes of covalently closed, nicked and gapped DNA minicircles, we conclude that 94-bp-long covalently closed and nicked DNA minicircles do not show sharp kinks while gapped DNA molecules, containing very flexible single-stranded regions, do show sharp kinks. We corroborate the results of cryo-EM studies by using Bal31 nuclease to probe for the existence of kinks in 94-bp-long minicircles.