Influence of the environment and probes on rapid DNA sequencing via transverse electronic transport

We study theoretically the feasibility of using transverse electronic transport within a nanopore for rapid DNA sequencing. Specifically, we examine the effects of the environment and detection probes on the distinguishability of the DNA bases. We find that the intrinsic measurement bandwidth of the electrodes helps the detection of single bases by averaging over the current distributions of each base. We also find that although the overall magnitude of the current may change dramatically with different detection conditions, the intrinsic distinguishability of the bases is not significantly affected by pore size and transverse field strength. The latter is the result of very effective stabilization of the DNA by the transverse field induced by the probes, so long as that field is much larger than the field that drives DNA through the pore. In addition, the ions and water together effectively screen the charge on the nucleotides, so that the electron states participating in the transport properties of the latter ones resemble those of the uncharged species. Finally, water in the environment has negligible direct influence on the transverse electrical current.Comment: 14 pages, 5 figure

Tautomeric mutation: A quantum spin modelling

A quantum spin model representing tautomeric mutation is proposed for any DNA molecule. Based on this model, the quantum mechanical calculations for mutational rate and complementarity restoring repair rate in the replication processes are carried out. A possible application to a real biological system is discussed.Comment: 7 pages (no figures

On the nonlinear dynamics of topological solitons in DNA

Dynamics of topological solitons describing open states in the DNA double helix are studied in the frameworks of the model which takes into account asymmetry of the helix. It is shown that three types of topological solitons can occur in the DNA double chain. Interaction between the solitons, their interactions with the chain inhomogeneities and stability of the solitons with respect to thermal oscillations are investigated.Comment: 16 pages, 16 figure

Base pair opening and bubble transport in a DNA double helix induced by a protein molecule in a viscous medium

We study the nonlinear dynamics of a protein-DNA molecular system by treating DNA as a set of two coupled linear chains and protein in the form of a single linear chain sliding along the DNA at the physiological temperature in a viscous medium. The nonlinear dynamics of the above molecular system in general is governed by a perturbed nonlinear Schr\"{o}dinger equation. In the non-viscous limit, the equation reduces to the completely integrable nonlinear Schr\"{o}dinger (NLS) equation which admits N-soliton solutions. The soliton excitations of the DNA bases make localized base pair opening and travel along the DNA chain in the form of a bubble. This may represent the bubble generated during the transcription process when an RNA-polymerase binds to a promoter site in the DNA double helical chain. The perturbed NLS equation is solved using a perturbation theory by treating the viscous effect due to surrounding as a weak perturbation and the results show that the viscosity of the solvent in the surrounding damps out the amplitude of the soliton.Comment: 4. Submitted to Phys. Rev.

Positional, Reorientational and Bond Orientational Order in DNA Mesophases

We investigate the orientational order of transverse polarization vectors of long, stiff polymer molecules and their coupling to bond orientational and positional order in high density mesophases. Homogeneous ordering of transverse polarization vector promotes distortions in the hexatic phase, whereas inhomogeneous ordering precipitates crystalization of the 2D sections with different orientations of the transverse polarization vector on each molecule in the unit cell. We propose possible scenarios for going from the hexatic phase, through the distorted hexatic phase to the crystalline phase with an orthorhombic unit cell observed experimentally for the case of DNA.Comment: 4 pages, 2 figure

Two-phase stretching of molecular chains

While stretching of most polymer chains leads to rather featureless force-extension diagrams, some, notably DNA, exhibit non-trivial behavior with a distinct plateau region. Here we propose a unified theory that connects force-extension characteristics of the polymer chain with the convexity properties of the extension energy profile of its individual monomer subunits. Namely, if the effective monomer deformation energy as a function of its extension has a non-convex (concave up) region, the stretched polymer chain separates into two phases: the weakly and strongly stretched monomers. Simplified planar and 3D polymer models are used to illustrate the basic principles of the proposed model. Specifically, we show rigorously that when the secondary structure of a polymer is mostly due to weak non-covalent interactions, the stretching is two-phase, and the force-stretching diagram has the characteristic plateau. We then use realistic coarse-grained models to confirm the main findings and make direct connection to the microscopic structure of the monomers. We demostrate in detail how the two-phase scenario is realized in the \alpha-helix, and in DNA double helix. The predicted plateau parameters are consistent with single molecules experiments. Detailed analysis of DNA stretching demonstrates that breaking of Watson-Crick bonds is not necessary for the existence of the plateau, although some of the bonds do break as the double-helix extends at room temperature. The main strengths of the proposed theory are its generality and direct microscopic connection.Comment: 16 pges, 22 figure

Colloquium: Physical approaches to DNA sequencing and detection

With the continued improvement of sequencing technologies, the prospect of genome-based medicine is now at the forefront of scientific research. To realize this potential, however, a revolutionary sequencing method is needed for the cost-effective and rapid interrogation of individual genomes. This capability is likely to be provided by a physical approach to probing DNA at the single-nucleotide level. This is in sharp contrast to current techniques and instruments that probe (through chemical elongation, electrophoresis, and optical detection) length differences and terminating bases of strands of DNA. Several physical approaches to DNA detection have the potential to deliver fast and low-cost sequencing. Central to these approaches is the concept of nanochannels or nanopores, which allow for the spatial confinement of DNA molecules. In addition to their possible impact in medicine and biology, the methods offer ideal test beds to study open scientific issues and challenges in the relatively unexplored area at the interface between solids, liquids, and biomolecules at the nanometer length scale. This Colloquium emphasizes the physics behind these methods and ideas, critically describes their advantages and drawbacks, and discusses future research opportunities in the field