Showing papers on "Molecular models of DNA published in 2005"

Nucleic acid nanostructures: Bottom-up control of geometry on the nanoscale

Abstract: DNA may seem an unlikely molecule from which to build nanostructures, but this is not correct. The specificity of interaction that enables DNA to function so successfully as genetic material also enables its use as a smart molecule for construction on the nanoscale. The key to using DNA for this purpose is the design of stable branched molecules, which expand its ability to interact specifically with other nucleic acid molecules. The same interactions used by genetic engineers can be used to make cohesive interactions with other DNA molecules that lead to a variety of new species. Branched DNA molecules are easy to design, and they can assume a variety of structural motifs. These can be used for purposes both of specific construction, such as polyhedra, and for the assembly of topological targets. A variety of two-dimensional periodic arrays with specific patterns have been made. DNA nanomechanical devices have been built with a series of different triggers, small molecules, nucleic acid molecules and proteins. Recently, progress has been made in self-replication of DNA nanoconstructs, and in the scaffolding of other species into DNA arrangements.

DNA Enables Nanoscale Control of the Structure of Matter

Abstract: Structural DNA nanotechnology consists of constructing objects, lattices and devices from branched DNA molecules. Branched DNA molecules open the way for the construction of a variety of N-connected motifs. These motifs can be joined by cohesive interactions to produce larger constructs in a bottom-up approach to nanoconstruction. The first objects produced by this approach were stick polyhedra and topological targets, such as knots and Borromean rings. These were followed by periodic arrays with programmable patterns. It is possible to exploit DNA structural transitions and sequence-specific binding to produce a variety of DNA nanomechanical devices, which include a bipedal walker and a machine that emulates the translational capabilities of the ribosome. Much of the promise of this methodology involves the use of DNA to scaffold other materials, such as biological macromolecules, nanoelectronic components, and polymers. These systems are designed to lead to improvements in crystallography, computation and the production of diverse and exotic materials.

DNA constraints allow rational control of macromolecular conformation.

Abstract: We report that double-helical DNA constraints can be used to control the conformation of another molecule, RNA. When a covalently attached DNA constraint is structurally incompatible with the native Mg2+-dependent RNA conformation, RNA folding is disrupted, as revealed by nondenaturing gel electrophoresis and independently by chemical probing. Our approach is distinct from other efforts in DNA nanotechnology, which have prepared DNA objects by self-assembly, built static DNA lattices for assembly of other objects, and created nanomachines made solely of DNA. In contrast, our dynamic use of DNA to control the conformations of other macromolecules should have wide impact in nanotechnology applications ranging from materials science to biology.

Normal-Mode Analysis of Circular DNA at the Base-Pair Level. 2. Large-Scale Configurational Transformation of a Naturally Curved Molecule.

Abstract: Fine structural and energetic details embedded in the DNA base sequence, such as intrinsic curvature, are important to the packaging and processing of the genetic material. Here we investigate the internal dynamics of a 200 bp closed circular molecule with natural curvature using a newly developed normal-mode treatment of DNA in terms of neighboring base-pair "step" parameters. The intrinsic curvature of the DNA is described by a 10 bp repeating pattern of bending distortions at successive base-pair steps. We vary the degree of intrinsic curvature and the superhelical stress on the molecule and consider the normal-mode fluctuations of both the circle and the stable figure-8 configuration under conditions where the energies of the two states are similar. To extract the properties due solely to curvature, we ignore other important features of the double helix, such as the extensibility of the chain, the anisotropy of local bending, and the coupling of step parameters. We compare the computed normal modes of the curved DNA model with the corresponding dynamical features of a covalently closed duplex of the same chain length constructed from naturally straight DNA and with the theoretically predicted dynamical properties of a naturally circular, inextensible elastic rod, i.e., an O-ring. The cyclic molecules with intrinsic curvature are found to be more deformable under superhelical stress than rings formed from naturally straight DNA. As superhelical stress is accumulated in the DNA, the frequency, i.e., energy, of the dominant bending mode decreases in value, and if the imposed stress is sufficiently large, a global configurational rearrangement of the circle to the figure-8 form takes place. We combine energy minimization with normal-mode calculations of the two states to decipher the configurational pathway between the two states. We also describe and make use of a general analytical treatment of the thermal fluctuations of an elastic rod to characterize the motions of the minicircle as a whole from knowledge of the full set of normal modes. The remarkable agreement between computed and theoretically predicted values of the average deviation and dispersion of the writhe of the circular configuration adds to the reliability in the computational approach. Application of the new formalism to the computed modes of the figure-8 provides insights into macromolecular motions which are beyond the scope of current theoretical treatments.

Course 7 Introduction to single-DNA micromechanics

Abstract: Publisher Summary This chapter discusses introduction to Single-Deoxyribonucleic Acid (DNA) micromechanics Over the past ten years new single-molecule techniques to study individual biomolecules have been developed Many of the new approaches being used are based on micromanipulation of single DNAs, allowing direct study of DNA, and enzymes which interact with it These lectures focus on mechanical properties of DNA, crucial to the design and interpretation of single-DNA experiments, and to the understanding of how DNA is processed and therefore, functions inside the cell DNA has extremely interesting and unique polymer properties In double helix form it is a water-soluble, semiflexible polymer which can be obtained in gigantic lengths The double helix (sometimes called the “B-form”) is taken by DNA most of the time in the cell This form of DNA has a regular helical structure with remarkably uniform mechanical properties The double helix is made of two DNA polymer molecules Each DNA polymer is a string of four interchangeable types of monomers, which can be strung together in any sequence

A 3D Model of Double-Helical DNA Showing Variable Chemical Details

Abstract: Since the first DNA model was created ≈50 years ago using molecular models, students and teachers have been building simplified DNA models from various practical materials. A 3D double-helical DNA model, made by placing beads on a wire and stringing beads through holes in plastic canvas, is described. Suggestions are given to enhance the basic helical frame to show the shapes and sizes of the nitrogenous base rings, 3′ and 5′ chain termini, and base pair hydrogen bonding. Students can incorporate random or real gene sequence data into their models. One example of a gene sequence, for the protein oxytocin, is given. Left-handed Z-DNA, as well as right-handed A-DNA and B-DNA models can be constructed. Aimed for use in high school science classes, it takes 2–3 hours to complete DNA models with 30 labeled base pairs. Photos of oxytocin models are included. The size of this sturdy model is appropriate for visually-impaired students to feel the helical shape and read the genetic code in Braille. This model is i...

Course 6 Single-molecule studies of DNA mechanics and DNA/Protein interactions

Abstract: Publisher Summary This chapter discusses single-molecule studies of Deoxyribonucleic Acid (DNA) mechanics and DNA/protein interactions. Physicists are interested in DNA for several reasons. First of all, it is a unique polymer characterized by incredible lengths (up to several centimeters per molecule in the case of human chromosomes) and a very high degree of monodispersity. If certain artificial polymers, such as polystyrene or polyethylene glycol are capable of achieving high degrees of polymerization, it is still very difficult to impose a specific length for the whole sample. Moreover, these artificial polymers are not very rigid at the scale of the monomer; it is shown in the chapter, DNA are more rigid, is (paradoxically) much easier to stretch out. Another important point is that DNA is, for now, the only polymer that may be easily modified and observed by scientists. An ever-growing number of tools in molecular biology-restriction enzymes, ligases, PCR, electrophoresis gels make it possible to cut, reglue, modify, and purify DNA fragments in a manner that is both simple and precise. One can readily obtain large numbers of DNA molecules, each one of them bearing the exact same modifications at the exact same position.

Course 1 DNA structure, dynamics and recognition

Abstract: Publisher Summary This chapter discusses Deoxyribonucleic Acid (DNA) structure, dynamics, and recognition. Despite the very real complexity of cellular functioning, the sequencing of entire genomes means that it is becoming feasible, at least for the simplest organisms, to build lists of all the proteins encoded in the DNA message, to understand how the production of these proteins is controlled (initially through the subtle interplay of the proteins, known as “transcription factors,” controlling DNA→RNA transcription), and how these proteins interact with one another or act upon other molecules present within the cell, leading to energy storage, molecular synthesis, and so on. Converting the chemical structure of DNA into a molecular conformation turned out to be a difficult task. A key step involved obtaining X-ray diffraction patterns for fibers, which could be easily pulled by inserting a glass rod into a solution of DNA. Although X-ray diffraction is the best technique available for determining the fine structure of DNA, the very process of forming crystals does run the risk of deforming the oligomers.

DNA/protein modeling

Abstract: Considerable progress has been made in modeling both DNA and protein-DNA complexes. The results help explain how specific base sequences can modify the properties of the double helix, influencing its structure and mechanical properties. These changes are important for the understanding of DNA recognition and packing. In the case of protein-DNA complexes, modeling can help in identifying protein-binding sites and in understanding the consequences of mutations in either of the interacting partners. Modeling can also be used to obtain structural and dynamic information from a variety of experimental data and will also contribute to extending the nanotechnological applications of the double helix. Keywords: DNA; protein-DNA; molecular modeling; molecular dynamics; DNA curvature; DNA packing; elastic rod; binding specificity; weight matrix

DNA conformation and transcriptional properties: a higher-order of silence

Abstract: Various kinds of chemical species can induce DNA molecules collapse from an unfolded, random-coiled state to a folded, compact and ordered state This phenomenon has been interpreted in terms of DNA condensation or compaction, and can be achieved in physiological-mimetic conditions We performed experiments on a variety of templates in order to assess the influence of DNA conformation, or higher-order structure, on transcriptional reactivity DNA length appears as a critical parameter for plausible large-scale genetic activity regulation mechanisms