Showing papers on "Molecular models of DNA published in 2010"

Nanomaterials based on DNA.

Abstract: The combination of synthetic stable branched DNA and sticky-ended cohesion has led to the development of structural DNA nanotechnology over the past 30 years. The basis of this enterprise is that it is possible to construct novel DNA-based materials by combining these features in a self-assembly protocol. Thus, simple branched molecules lead directly to the construction of polyhedrons, whose edges consist of double helical DNA and whose vertices correspond to the branch points. Stiffer branched motifs can be used to produce self-assembled two-dimensional and three-dimensional periodic lattices of DNA (crystals). DNA has also been used to make a variety of nanomechanical devices, including molecules that change their shapes and molecules that can walk along a DNA sidewalk. Devices have been incorporated into two-dimensional DNA arrangements; sequence-dependent devices are driven by increases in nucleotide pairing at each step in their machine cycles.

Single-molecule chemical reactions on DNA origami

Abstract: DNA nanotechnology and particularly DNA origami, in which long, single-stranded DNA molecules are folded into predetermined shapes, can be used to form complex self-assembled nanostructures. Although DNA itself has limited chemical, optical or electronic functionality, DNA nanostructures can serve as templates for building materials with new functional properties. Relatively large nanocomponents such as nanoparticles and biomolecules can also be integrated into DNA nanostructures and imaged. Here, we show that chemical reactions with single molecules can be performed and imaged at a local position on a DNA origami scaffold by atomic force microscopy. The high yields and chemoselectivities of successive cleavage and bond-forming reactions observed in these experiments demonstrate the feasibility of post-assembly chemical modification of DNA nanostructures and their potential use as locally addressable solid supports.

Folding and cutting DNA into reconfigurable topological nanostructures

Abstract: Topology is the mathematical study of the spatial properties that are preserved through the deformation, twisting and stretching of objects. Topological architectures are common in nature and can be seen, for example, in DNA molecules that condense and relax during cellular events1. Synthetic topological nanostructures, such as catenanes and rotaxanes, have been engineered using supramolecular chemistry, but the fabrication of complex and reconfigurable structures remains challenging2. Here, we show that DNA origami3 can be used to assemble a Mobius strip, a topological ribbon-like structure that has only one side4,5,6. In addition, we show that the DNA Mobius strip can be reconfigured through strand displacement7 to create topological objects such as supercoiled ring and catenane structures. This DNA fold-and-cut strategy, analogous to Japanese kirigami8, may be used to create and reconfigure programmable topological structures that are unprecedented in molecular engineering. A Mobius strip — a ribbon-like structure with only one side — can be assembled from DNA origami and then reconfigured into various topologies by cutting along the length of the strip.

DNA curvature and flexibility in vitro and in vivo

Abstract: It has been more than 50 years since the elucidation of the structure of double-helical DNA. Despite active research and progress in DNA biology and biochemistry, much remains to be learned in the field of DNA biophysics. Predicting the sequence-dependent curvature and flexibility of DNA is difficult. Applicability of the conventional worm-like chain polymer model of DNA has been challenged. The fundamental forces responsible for the remarkable resistance of DNA to bending and twisting remain controversial. The apparent 'softening' of DNA measured in vivo in the presence of kinking proteins and superhelical strain is incompletely understood. New methods and insights are being applied to these problems. This review places current work on DNA biophysics in historical context and illustrates the ongoing interplay between theory and experiment in this exciting field.

Development of coarse-graining DNA models for single-nucleotide resolution analysis.

Abstract: Recently, analytical techniques have been developed for detecting single-nucleotide polymorphisms in DNA sequences. Improvements of the sequence identification techniques has attracted much attention in several fields. However, there are many things that have not been clarified about DNA. In the present study, we have developed a coarsegraining DNA model with single-nucleotide resolution, in which potential functions for hydrogen bonds and the p-stack effect are taken into account. Using Langevin-dynamics simulations, several characteristics of the coarse-grained DNA have been clarified. The validity of the present model has been confirmed, compared with other experimental and computational results. In particular, the melting temperature and persistence length are in good agreement with the experimental results for a wide range of salt concentrations.

Single-Molecule DNA Analysis

Abstract: The ability to detect single molecules of DNA or RNA has led to an extremely rich area of exploration of the single most important biomolecule in nature. In cases in which the nucleic acid molecules are tethered to a solid support, confined to a channel, or simply allowed to diffuse into a detection volume, novel techniques have been developed to manipulate the DNA and to examine properties such as structural dynamics and protein-DNA interactions. Beyond the analysis of the properties of nucleic acids themselves, single-molecule detection has enabled dramatic improvements in the throughput of DNA sequencing and holds promise for continuing progress. Both optical and nonoptical detection methods that use surfaces, nanopores, and zero-mode waveguides have been attempted, and one optically based instrument is already commercially available. The breadth of literature related to single-molecule DNA analysis is vast; this review focuses on a survey of efforts in molecular dynamics and nucleic acid sequencing.

Coarse‐grained molecular dynamics modeling of DNA–carbon nanotube complexes

Abstract: We present a coarse-grained method to study the energetics and morphologies of DNA–carbon nanotube (DNA-CNT) complexes in aqueous environment. In this method, we adopt an existing coarse-grained DNA model in which each nucleotide is coarse-grained by two interaction sites, one for the phosphate and sugar groups and the other for the base group. The interaction potentials between DNA sites and the carbon atoms on a CNT are parameterized through all-atom molecular dynamics (MD) simulations. The water molecules are treated implicitly using Langevin dynamics. The coarse-grained DNA-CNT model significantly improves the computational affordability, while captures the essential dynamics of DNA-CNT interactions observed from all-atom MD simulations. The coarse-grained method enables us to efficiently simulate adhesion, encapsulation, and wrapping processes of a single-stranded DNA molecule around CNTs. The simulation results agree with those obtained by all-atom MD simulations in several aspects. Our coarse-grained simulations provide useful guidelines in positioning DNA molecules on a CNT surface or graphene substrate in single-molecule experimental studies. Copyright © 2009 John Wiley & Sons, Ltd.

Macroscopic localization lengths of vibrational normal modes in a heuristic DNA model

Abstract: In this work we study the localization of vibrational modes in heuristic models for disordered DNA-like molecules. Within such approach, atomic groups are replaced by renormalized sites connected by effective springs. The oscillation amplitudes at each site are considered and the localization degree of the normal modes is analyzed by means of the participation ratio, as well as the relative fluctuation of an ensemble of disorder realizations for normal modes in different frequency ranges. The present results suggest that the dynamical properties at low frequencies are completely different for double-strand structures compared to single-strand ones. Irrespective to disorder, double-strand molecules show normal modes with macroscopic localization lengths at low frequencies, for a wide range of spring constants considered in the literature, in contrast to the strong localization in single strands.

Stationary solutions for a modified Peyrard-Bishop DNA model with up to third-neighbor interactions

Abstract: We investigate a DNA model that takes into account stacking interactions with neighbors up to three bases away. The model is a generalization of the well-known Peyrard-Bishop (PB) model and is motivated by studies that suggest that nearest-neighbor models for base-pair interaction in a DNA chain might not be enough to capture the mechanism and dynamics of DNA base-pair opening. We study stationary solutions of the modified model and investigate their stability. A comparison with the PB model reveals that under a wide range of parameter values the main characteristics of the original model --such as the hyperbolicity of the equilibrium at the origin-- are preserved, but new types of stationary solutions emerge.

Modulation of electronic structures of bases through DNA recognition of protein

Abstract: The effects of environmental structures on the electronic states of functional regions in a fully solvated complex were investigated using combined ab initio quantum mechanics/molecular mechanics calculations. A complex of a transcriptional factor, PU.1, and the target DNA was used for the calculations. The effects of solvent on the energies of molecular orbitals (MOs) of some DNA bases strongly correlate with the magnitude of masking of the DNA bases from the solvent by the protein. In the complex, PU.1 causes a variation in the magnitude among DNA bases by means of directly recognizing the DNA bases through hydrogen bonds and inducing structural changes of the DNA structure from the canonical one. Thus, the strong correlation found in this study is the first evidence showing the close quantitative relationship between recognition modes of DNA bases and the energy levels of the corresponding MOs. Thus, it has been revealed that the electronic state of each base is highly regulated and organized by the DNA recognition of the protein. Other biological macromolecular systems can be expected to also possess similar modulation mechanisms, suggesting that this finding provides a novel basis for the understanding for the regulation functions of biological macromolecular systems.

From nucleosomes to chromatin fibers: molecular dynamics and Monte Carlo simulations of nucleosome organization and interactions

Abstract: Chromosomes consist of a chain of nucleosomes, in which DNA wraps almost twice around a histone protein core. Nucleosomes are stable complexes and their position along the DNA regulates DNA accessibility. The underlying mechanisms of this process are still not understood well. In this thesis, molecular dynamics, steered molecular dynamics and Monte Carlo simulations were conducted to elucidate nucleosome organization and the folding of nucleosome chains into chromatin fibers at different length scales. The all-atom resolution of molecular dynamics simulations revealed a novel map of histone-DNA interaction sites extending experimental findings. By applying external forces the complete DNA unwrapping from the protein core at atomic resolution was investigated. This revealed intermediates of the pathway and an important contribution of the unstructured histone tails to nucleosome stability. Simulations of stretching coarse-grained chromatin fibers showed that experimental force-extension curves alone are insufficient to identify fiber geometry parameters and internucleosomal interaction strength. The chromatin fiber model was extended by a new description for DNA electrostatics to enable the translocation of nucleosomes within the fiber. The effect of this process on the stability of the fiber was strongly dependent on its geometry.

Electron transport through one and four-channel DNA models

Abstract: DNA molecules possess high density genetic information in living beings, as well as selfassembly and self-recognition properties that make them excellent candidates for many scientific areas, from medicine to nanotechnology. The process of electron transport through DNA is important because DNA repair occurs spontaneously via the process that restores mismatches and lesions, and furthermore, DNA-based molecular electronics in nano-bioelectronics can be possible through the process. In this thesis, we study theoretically the transport properties through a one-dimensional one-channel DNA model, a quasi-one-dimensional one-channel DNA model, and a two-dimensional four-channel DNA model by using the Tight-Binding Hamiltonian method. We show graphical outputs of the transmission, overall contour plots of transmission, localization lengths, the Lyapunov exponent, and current-voltage characteristics as a function of incoming electron energy and magnetic flux which are obtained using Mathematica run on the CSH Beowulf Cluster. Our results show that the semiconductor behavior can be observed in the I-V characteristics. The current through a quasi-one-dimensional one-channel DNA model starts to flow after the breakdown voltage and remains constant after threshold voltage. The variations of the temperature make the fluctuations of the system. As the temperature increases, the sharp transmission resonances are smeared out and the localization lengths are also decreased. Due to a magnetic field penetrating at the center of the two-dimensional DNA model, the Aharonov- Bohm (AB) oscillations can be observed.