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Showing papers on "Molecular models of DNA published in 2008"


Journal ArticleDOI
TL;DR: The results demonstrate that conformational flexibility could be explored to generate complex DNA nanostructures and might be further extended to other biomacromolecular systems, such as RNA and proteins.
Abstract: Molecular self-assembly is a promising approach to the preparation of nanostructures. DNA, in particular, shows great potential to be a superb molecular system. Synthetic DNA molecules have been programmed to assemble into a wide range of nanostructures. It is generally believed that rigidities of DNA nanomotifs (tiles) are essential for programmable self-assembly of well defined nanostructures. Recently, we have shown that adequate conformational flexibility could be exploited for assembling 3D objects, including tetrahedra, dodecahedra, and buckyballs, out of DNA three-point star motifs. In the current study, we have integrated tensegrity principle into this concept to assemble well defined, complex nanostructures in both 2D and 3D. A symmetric five-point-star motif (tile) has been designed to assemble into icosahedra or large nanocages depending on the concentration and flexibility of the DNA tiles. In both cases, the DNA tiles exhibit significant flexibilities and undergo substantial conformational changes, either symmetrically bending out of the plane or asymmetrically bending in the plane. In contrast to the complicated natures of the assembled structures, the approach presented here is simple and only requires three different component DNA strands. These results demonstrate that conformational flexibility could be explored to generate complex DNA nanostructures. The basic concept might be further extended to other biomacromolecular systems, such as RNA and proteins.

266 citations


Journal ArticleDOI
TL;DR: The design, construction and structural analysis of a covalently closed and stable 3D DNA structure with the connectivity of an octahedron that assembles from eight oligonucleotides with a yield of ∼30%.
Abstract: The inherent properties of DNA as a stable polymer with unique affinity for partner molecules determined by the specific Watson-Crick base pairing makes it an ideal component in self-assembling structures. This has been exploited for decades in the design of a variety of artificial substrates for investigations of DNA-interacting enzymes. More recently, strategies for synthesis of more complex two-dimensional (2D) and 3D DNA structures have emerged. However, the building of such structures is still in progress and more experiences from different research groups and different fields of expertise are necessary before complex DNA structures can be routinely designed for the use in basal science and/or biotechnology. Here we present the design, construction and structural analysis of a covalently closed and stable 3D DNA structure with the connectivity of an octahedron, as defined by the double-stranded DNA helices that assembles from eight oligonucleotides with a yield of approximately 30%. As demonstrated by Small Angle X-ray Scattering and cryo-Transmission Electron Microscopy analyses the eight-stranded DNA structure has a central cavity larger than the apertures in the surrounding DNA lattice and can be described as a nano-scale DNA cage, Hence, in theory it could hold proteins or other bio-molecules to enable their investigation in certain harmful environments or even allow their organization into higher order structures.

128 citations


Journal ArticleDOI
TL;DR: In this article, the authors present recent progress in development of low-energy electron tracks in condensed media and high-energy proton tracks and discuss progress in characterizing DNA damage in terms of types and complexity.

65 citations


Journal ArticleDOI
TL;DR: A new one-bead-per-nucleotide coarse-grained model that combines structural accuracy and predictive power, achieved by means of the accurate choice of the force field terms and their unbiased statistically based parametrization is reported.
Abstract: We report molecular dynamics simulations of DNA nanocircles and submicrometer-sized plasmids with torsional stress. The multiple microseconds time scale is reached thanks to a new one-bead-per-nucleotide coarse-grained model that combines structural accuracy and predictive power, achieved by means of the accurate choice of the force field terms and their unbiased statistically based parametrization. The model is validated with experimental structural data and available all-atom simulations of DNA nanocircles. Besides reproducing the nanocircles' structures and behavior on the short time scale, our model is capable of exploring three orders of magnitude further in time and to sample more efficiently the configuration space, unraveling novel behaviors. We explored the microsecond dynamics of entire small plasmids and observed supercoiling and compaction in the overtwisted case. The stability of overtwisted nanocircles and plasmids is predicted up to macroscopic time scales. Conversely, in the undertwisted case, at physiological values of the superhelical density, after a metastable phase of supercoiling-compaction, we observe the formation and the complex dynamics of denaturation bubbles over a multiple microseconds time scale. Our results indicate that the torsional stress is involved in a delicate balance with the temperature to determine the denaturation equilibrium and regulate the transcription process.

40 citations


Journal ArticleDOI
TL;DR: Results show that the protein indirect DNA readout is not only addressable to the DNA molecule flexibility but it is finely tuned by the mechanical and dynamical properties of the protein scaffold involved in the interaction.

13 citations


Journal ArticleDOI
TL;DR: It is demonstrated by transmission electron microscopy that the DNA parallelogram motif and the bulged-junction DNA triangle are deformed by the presence of the gold nanoparticles, whereas the structure of the 3D-DX DNA triangle motif appears to be minimally distorted.

13 citations


Journal ArticleDOI
TL;DR: By studying the eigenstates' symmetries in uniform and nonuniform DNA chains, it is concluded that, in both cases, the transitions are almost vertical in K space, which can provide an insight into the electronic band structure of DNA.
Abstract: We analyze the band structure and interband optical transitions in a dangling backbone ladder DNA model. Using this model, semiconducting synthetic poly(G)- poly(C) DNA is studied by means of a tight-binding model traditionally used for transport studies. Numerical calculations for optical absorption spectra are also presented. By studying the eigenstates' symmetries in uniform and nonuniform DNA chains, we conclude that, in both cases, the transitions are almost vertical in K space. The optical gap turns out larger than the electronic one, and an indirect band gap electronic structure for this DNA model is revealed. The effects of the environment, which are relevant for the wet form of DNA, are taken into account by introducing disorder in the backbone levels. We demonstrate that they affect more the spectra in the case of parallel polarization of the incoming light (with respect to the molecule axis). In such a case, the closure of the gap appears for a large enough disorder. We also consider the natural helix DNA conformation and find unusual selection rules for interband optical transitions. We propose that a comparison between the obtained spectra and the experiments can provide an insight into the electronic band structure of DNA.

12 citations


Journal ArticleDOI
TL;DR: The presently accessible durations of MD trajectories provide reasonably accurate evaluation of DNA elasticity and allow modeling of its mesoscopic properties and good qualitative agreement with the worm-like chain (WLC) theory is reached in MD.
Abstract: The paper considers statistical properties of ensembles of chain conformations obtained by short-time Brownian dynamics (BD) of a coarse-grained DNA model in order to find out if the conditions necessary for accurate evaluation of the polymer elasticity are attainable in atom-level molecular dynamics (MD) simulations. To measure the bending persistence length (PL) with a 10% error using data accumulated in a single trajectory of a double helix of 15 base pairs, dynamics should be continued for a few microseconds. However, these estimates should be scaled down by about 2 orders of magnitude because the bending dynamics of short double helices in MD features much smaller relaxation times. As a result, good qualitative agreement with the worm-like chain (WLC) theory is reached in MD after tens of nanoseconds. The presently accessible durations of MD trajectories provide reasonably accurate evaluation of DNA elasticity and allow modeling of its mesoscopic properties. The surprisingly fast bending dynamics of short double helices in MD suggests that the microscopic mechanisms of DNA flexibility differ from a simple harmonic model.

10 citations


01 Jan 2008
TL;DR: This work uses single DNA molecule stretching to investigate the degree of alteration in the structure and stability of DNA in the presence of DNA binding proteins which help to quantify thermodynamics and kinetics of protein-protein and protein-nucleic acid interactions and obtain new insights into the function of proteins in these specific biological system.
Abstract: The process of replication requires the cooperation of many proteins which associate with each other at the replication fork to form a highly efficient replication machine. Bacterium E. coli and bacteriophages that infect it (T4 and T7) have been used extensively in molecular biology research and provide excellent model systems for analyzing the DNA replication. In this work we use single DNA molecule stretching to investigate the degree of alteration in the structure and stability of DNA in the presence of DNA binding proteins which help us to quantify thermodynamics and kinetics of protein-protein and protein-nucleic acid interactions and obtain new insights into the function of proteins in these specific biological system. Because the nature of the overstretching transition in DNA stretching experiments continues to generate controversy we have undertaken studies of DNA stretching in the presence of glyoxal to solve this dilemma which brought new evidence in favor of force-induced melting theory against the alternative S-DNA model. One of the classic paradigms of single-stranded DNA binding proteins is bacteriophage T7 gene 2.5 protein (gp2.5), known to have essential roles in DNA replication and recombination in phage-infected cells by binding preferentially to single-stranded DNA and establishing electrostatic interactions with other proteins, recruiting them at the site of the ssDNA and regulating their activity. Varying solution conditions and the pulling dynamics, we could obtain binding affinities to single- and double-stranded DNA for gp2.5 and its deletion mutant lacking 26 C-terminal residues, gp2.5-Δ26C, over a range of salt concentration not available to ensemble studies. We also

3 citations


Proceedings ArticleDOI
19 Dec 2008
TL;DR: It is not convenient to use separate or multi-separate operations of sticker DNA model directly in Adleman-Lipton model, so the Extended Separate technology was proposed originally and the biochemical implementing method was given; and the feasibilities and validities of the algorithms were proved.
Abstract: It is not convenient to use separate or multi-separate operations of sticker DNA model directly in Adleman-Lipton model. In order to make experiments conveniently in Adleman-Lipton model, the Extended Separate technology was proposed originally; and the biochemical implementing method was given, too. Both a sticker DNA algorithm of linear full permutation problem (LIFPP) and a sticker DNA algorithm of circle full permutation problem (CIFPP) were proposed based on the vast parallelism and large message-storage capacity of sticker DNA model; and the differences between the algorithms were illustrated, too. The operation steps of the two algorithms were given through an instance; and the biochemical processes were illustrated by simulation experiments. The final correct results were gotten through the simulation experiments. Consequently, the feasibilities and validities of the algorithms were proved. At last, the operation complexities of the algorithms were analyzed.

2 citations


Proceedings ArticleDOI
07 May 2008
TL;DR: The addition of the haptic model enables users to feel the stretching and twisting forces while manipulating the model through the PHANTOMreg Desktop haptic device and can serve as a good instructional aid for helping users to understand the molecular structure of DNA through effective visual representation and interactive manipulation.
Abstract: The science of haptics has received enormous attention in the last decade. One of the major application trends of haptics technology is data visualization and training. In this paper, we present our work towards developing a haptically enabled model for the structure of DNA. The graphic model of the DNA strand is made up of individual base pair models. The environment presents two views of the model: a global view that reflects the real stretching forces for a 5000 base pair strand and a 40 base pair portion of the strand to display the twisting of the molecules. The addition of the haptic model enables users to feel the stretching and twisting forces while manipulating the model through the PHANTOMreg Desktop haptic device. Since the interaction forces are in the piconewton range, the forces applied by/to the user are scaled accordingly. The model can serve as a good instructional aid for helping users to understand the molecular structure of DNA through effective visual representation and interactive manipulation. In incorporating more physical details, it may also have a future use in simulating protein and enzyme interactions with DNA.

Dissertation
13 Aug 2008
TL;DR: Results show that dendrimers bridge the entire spectrum of biological condensation agents from small cations, such as spermine/spermidine encountered in viruses, to the much larger histone proteins found in eukaryotic cells, and are expected to contribute towards the design of new vectors for DNA gene delivery.
Abstract: DNA compaction is the collapse of long DNA chains into well-organized condensates of complex, hierarchical nanostructure induced by the presence of cationic agents. Although much progress has been made in understanding underlying interaction mechanisms of in vivo DNA compaction, the interplay of the myriad compaction agents and their types of interactions with DNA still raise a wealth of unanswered, fundamental questions. In particular, the hierarchical organization of chromatin is widely unclear. There, the DNA is first wrapped around histone cores and the formed beads-on-a-string structure is successively shifted towards higher order forms of chromatin structure. The latter process involves linker histones as major antagonists.Here, new results are presented that are derived from bio-mimetic investigations of the simplest possible DNA compaction model system containing only dendrimers, which can be viewed as uniformly charged cationic nanospheres, and unspecific, polydisperse DNA. Small angle X-ray (micro-)diffraction is employed as a principle method of analysis that accesses relevant molecular length scales. Targeting a quantitative understanding of compaction mechanisms, X-ray (micro-)diffraction measurements performed under laminar flow conditions in hydrodynamic focusing microfluidic devices provides microscale control of the self-assembly process. In addition, the method enables time-resolved access to structure formation in situ, in particular to transient intermediate states.Utilizing the high level of control over dendrimer size and charge, DNA compaction is systematically tuned and analyzed in detail. Results show that dendrimers bridge the entire spectrum of biological condensation agents from small cations, such as spermine/spermidine encountered in viruses, to the much larger histone proteins found in eukaryotic cells. Despite its simplicity, the dendrimer/DNA system reproduces characteristic features of DNA compaction in vivo. In particular, PAMAM 6 dendrimers (having a size and charge comparable to histone core proteins) induce a complete wrapping of the DNA around the cation. As such, PAMAM 6/DNA entities are structurally artificial equivalents of nucleosome core particles. For cationic dendrimers having an intermediate size and charge, which is conveniently between that of small multivalent organic cations and larger histone-like proteins, an alternate route of DNA compaction aside from the established salt or macroion condensation is observed in microflow below the isoelectric point, where DNA is in excess of dendrimers.In addition, the phenomenon of charge-induced dendrimer swelling has been experimentally quantified in detail over a wide range of generations. Results clearly show highly predictable, charge-induced changes of the dendrimer conformation and therefore eliminate the discrepancy between theory and experiments that previously existed in literature.Besides artificial model-proteins, the interaction of linker histones H1 and DNA has been studied in microflow. The time-resolved access to struture formation dynamics clearly shows that the interaction of H1 with DNA is a two step process: an initial unspecific binding of H1 to DNA is followed by a rearrangement of molecules in the formed complexes. Results suggest that the conformational transition of H1 tails from their rather extended conformation, in aqueous solution, to their fully folded state, upon interaction with DNA, is most likely the motor of the conformational phase transition of H1/DNA assemblies.Results obtained in this thesis are expected to have a direct bearing on the understanding of the hierarchical organization of chromatin in vivo. Underlying concepts and techniques may be generalized and used to experimentally address also other relevant protein/DNA systems. Moreover, the studied systems are of inherent importance to the field of biotechnology and are expected to contribute towards the design of new vectors for DNA gene delivery.

LI Xiao-long1
01 Jan 2008
TL;DR: A novel DNA model based pairwise key establishment algorithm is presented for distributed sensor networks, which uses characteristics of the code of oligonucleotides in DNA strands for key predistribution and which has better security, lower communication costs and higher probability of direct pairwiseKey establishment.
Abstract: On the basis of KDC(key distribution center)and diversity of DNA molecules,an innovative DNA model for key predistribution and key predistribution scheme based on the new DNA model are proposed.And in addition,by combing with the good characteristics of key pool,a novel DNA model based pairwise key establishment algorithm is presented for distributed sensor networks,which uses characteristics of the code of oligonucleotides in DNA strands for key predistribution,and in which,any pair of nodes exchange DNA strands information and use the code of some oligonucleotide in the DNA strand as their actual pairwise key.Theoretical and experimental analyses show that,compared with those previous well-known polynomial-based and polynomial pool-based key predistribution models and pairwise key establishment algorithms,the newly proposed algorithm has better security,lower communication costs and higher probability of direct pairwise key establishment.So,it is a better and more efficient new pairwise key establishment algorithm suitable for distributed sensor networks.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the Z2 symmetry related with the two opposite directions of the winding: the left-handed (Z-type) and the right-handed windings.
Abstract: The denaturation transition of DNA molecules is numerically investigated with a focus on the Z2 symmetry related with the two opposite directions of the winding: the left-handed (Z-type) and the right-handed (B-type) windings. We extend the previous DNA model Hamiltonian to include a term that phenomenologically describes the tangential interaction, making the same twist direction favored by adjacent base pairs. Evoking the large strength of the tangential interaction, we reveal the Z2 symmetry nature of twist directions associated with the opening of DNA strands. We also observe that the boundary between the B-domain and the Z-domain is point-like, in accordance with a recent experimental result.