Cable dynamics applied to long-length scale mechanics of DNA
Sachin Goyal, Todd Lillian, Noel C. Perkins, Edgar Meyhofer
备注：
14 pages, 7 figures, An invited keynote speech, in CD-ROM Proceedings of Sixth International Symposium on Cable Dynamics, Charleston, SC, 19-22 Sept, 2005
This paper introduces the use of cable dynamics models as a means to explore the mechanics of DNA on long-length scales. It is on these length scales that DNA forms twisted and curved three-dimensional shapes known as supercoils and loops. These long-length scale DNA structures have a pronounced influence on the functions of this molecule within the cell including the packing of DNA in the cell nucleus, transcription, replication and gene repair. We provide a short background to the mechanics of DNA and suggest the logical connection to the mechanics of a low tension cable. A computational model is then summarized and example results are presented for DNA supercoiling and looping.
In this letter, we point out the inaccurate figures in a letter by Peyrard and Bishop, who investigated the statistical mechanics of a nonlinear model for DNA denaturation. We give the correct figures.
The DNA molecule, apart from carrying the genetic information, plays a crucial role in a variety of biological processes and find applications in drug design, nanotechnology and nanoelectronics. The molecule undergoes significant structural transitions under the influence of forces due to physiological and non-physiological environments. Here, we summarize the insights gained from simulations and single-molecule experiments on the structural transitions and mechanics of DNA under force, as well as its elastic properties, in various environmental conditions, and discuss appealing future directi…
In this review we focus on the idea of establishing connections between the mechanical properties of DNAligand complexes and the physical chemistry of DNA-ligand interactions. This type of connection is interesting because it opens the possibility of performing a robust characterization of such interactions by using only one experimental technique: single molecule stretching. Furthermore, it also opens new possibilities in comparing results obtained by very different approaches, in special when comparing single molecule techniques to ensemble-averaging techniques. We start the manuscript revie…
A unifying theory of the denaturation transition of DNA, driven by temperature T or induced by an external mechanical torque Gamma is presented. Our model couples the hydrogen-bond opening and the untwisting of the helicoidal molecular structure. We show that denaturation corresponds to a first-order phase transition from B-DNA to d-DNA phases and that the coexistence region is naturally parametrized by the degree of supercoiling sigma. The denaturation free energy, the temperature dependence of the twist angle, the phase diagram in the T,Gamma plane and isotherms in the sigma, Gamma plane are…
A simple model of DNA based on two interacting polymers has been used to study the unzipping of a double stranded DNA subjected to a periodic force. We propose a dynamical transition, where without changing the physiological condition, it is possible to bring DNA from the zipped/unzipped state to a new dynamic (hysteretic) state by varying the frequency of the applied force. Our studies reveal that the area of the hystersis loop grows with the same exponents as of the isotropic spin systems. These exponents are amenable to verification in the force spectroscopic experiments.
Molecular dynamics simulations are often used to provide feedback in the design workflow of DNA nanostructures. However, even with coarse-grained models, convergence of distributions from unbiased simulation is slow, limiting applications to equilibrium structural properties. Given the increasing interest in dynamic, reconfigurable, and deformable devices, methods that enable efficient quantification of large ranges of motion, conformational transitions, and mechanical deformation are critically needed. Metadynamics is an automated biasing technique that enables the rapid acquisition of molecu…
Transcription is the first step of gene expression, in which a particular segment of DNA is copied to RNA by the enzyme RNA polymerase (RNAP). Despite many details of the complex interactions between DNA and RNA synthesis disclosed experimentally, much of physical behavior of transcription remains largely unknown. Understanding torsional mechanics of DNA and RNAP together with its nascent RNA and RNA-bound proteins in transcription maybe the first step towards deciphering the mechanism of gene expression. In this study, based on the balance between viscous drag on RNA synthesis and torque resu…
Many physical systems can be mapped onto solved or "solvable" models of magnetism. In this work, we have mapped the statistical mechanics of columnar phases of ideally helical rigid DNA -- subject to the earlier found unusual, frustrated pair potential [A. A. Kornyshev and S. Leikin, J. Chem. Phys. 107, 3656 (1997)] -- onto an exotic, unknown variant of the XY model on a fixed or restructurable lattice. Here the role of the 'spin' is played by the azimuthal orientation of the molecules. We have solved this model using a Hartree-Fock approximation, ground state calculations, and finite temperat…
We propose a statistical mechanics model for DNA melting in which base stacking and pairing are explicitly introduced as distinct degrees of freedom. Unlike previous approaches, this model describes thermal denaturation of DNA secondary structure in the whole experimentally accessible temperature range. Base pairing is described through a zipper model, base stacking through an Ising model. We present experimental data on the unstacking transition, obtained exploiting the observation that at moderately low pH this transition is moved down to experimentally accessible temperatures. These measure…
The first level of folding of DNA in eukaryotes is provided by the so called '10 nm chromatin fibre', where DNA wraps around histone proteins (approx. 10 nm in size) to form nucleosomes, which go on to create a zig zagging bead on a string structure. In this work we present a 1 dimensional statistical mechanics model to study nucleosome positioning within one such 10 nm fibre. We focus on the case of genomic sheep DNA, and we start from effective potentials valid at infinite dilution and determined from high resolution in vitro salt dialysis experiments. We study positioning within a polynucle…
In this paper, we show that the coarse grain model for DNA, which has been proposed recently by Knotts, Rathore, Schwartz and de Pablo (J. Chem. Phys. 126, 084901 (2007)), can be adapted to describe the thermal and mechanical denaturation of long DNA sequences by adjusting slightly the base pairing contribution. The adjusted model leads to (i) critical temperatures for long homogeneous sequences that are in good agreement with both experimental ones and those obtained from statistical models, (ii) a realistic step-like denaturation behaviour for long inhomogeneous sequences, and (iii) critical…
We study the effects of the shear force on the rupture mechanism on a double stranded DNA. Motivated by recent experiments, we perform the atomistic simulations with explicit solvent to obtain the distributions of extension in hydrogen and covalent bonds below the rupture force. We obtain a significant difference between the atomistic simulations and the existing results in the iterature based on the coarse-grained models (theory and simulations). We discuss the possible reasons and improve the coarse-grained model by incorporating the consequences of semi-microscopic details of the nucleotide…
We studied the structure and mechanical properties of DNA i-motif nanowires by means of molecular dynamics computer simulations. We built up to 230 nm long nanowires, based on a repeated TC5 sequence from crystallographic data, fully relaxed and equilibrated in water. The unusual stacked C*C+ stacked structure, formed by four ssDNA strands arranged in an intercalated tetramer, is here fully characterized both statically and dynamically. By applying stretching, compression and bending deformation with the steered molecular dynamics and umbrella sampling methods, we extract the apparent Young's …
Understanding the damage of DNA bases from hydrogen abstraction by free OH radicals is of particular importance to reveal the effect of hydroxyl radicals produced by the secondary effect of radiation. Previous studies address the problem with truncated DNA bases as ab-initio quantum simulation required to study such electronic spin dependent processes are computationally expensive. Here, for the first time, we employ a multiscale and hybrid Quantum-Mechanical-Molecular-Mechanical simulation to study the interaction of OH radicals with guanine-deoxyribose-phosphate DNA molecular unit in the pre…
A model of self-avoiding walk with suitable constraints on self-attraction is developed to describe the conformational behavior of a short RNA or a single stranded DNA molecule that forms hairpin structure and calculate the properties associated with coil-hairpin transition by enumerating all possible conformations of a chain of N monomers in two and three dimensions. The first and last five monomers of the chain have been allowed to pair and form the stem of the hairpin structure while the remaining monomers can form a loop. The coil-hairpin transition is found to be first order with large en…
Rapid sequencing of individual human genome is prerequisite to genomic medicine, where diseases will be prevented by preemptive cures. Quantum-mechanical tunneling through single-stranded DNA in a solid-state nanopore has been proposed for rapid DNA sequencing, but unfortunately the tunneling current alone cannot distinguish the four nucleotides due to large fluctuations in molecular conformation and solvent. Here, we propose a machine-learning approach applied to the tunneling current-voltage (I-V) characteristic for efficient discrimination between the four nucleotides. We first combine prin…
We investigate the thermodynamics and kinetics of DNA hairpins that fold/unfold under the action of applied mechanical force. We introduce the concept of the molecular free energy landscape and derive simplified expressions for the force dependent Kramers-Bell rates. To test the theory we have designed a specific DNA hairpin sequence that shows two-state cooperative folding under mechanical tension and carried out pulling experiments using optical tweezers. We show how we can determine the parameters that characterize the molecular free energy landscape of such sequence from rupture force kine…
Bacteriophages infect cells by attaching to the outer membrane and injecting their DNA into the cell.The phage DNA is then transcribed by the cell's transcription machinery.A number of physical mechanisms by which DNA can be translocated from the phage capsid into the cell have been identified. A fast ejection driven by the elastic and electrostatic potential energy of the compacted DNA within the viral capsid appears to be used by most phages, at least to initiate infection.In recent in vitro experiments, the speed of DNA translocation from a lambda phage capsid has been measured as a functio…
The local mechanical properties of DNA are believed to play an important role in their biological functions and DNA-based nanomechanical devices. Using a simple sphere-tip compression system, the local radial mechanical properties of DNA are systematically studied by changing the tip size. The compression simulation results for the 16 nm diameter sphere tip are well consistent with the experimental results. With the diameter of the tip decreasing, the radial compressive elastic properties under external loads become sensitive to the tip size and the local DNA conformation. There appears a sudd…
A fundamental design rule that nature has developed for biological machines is the intimate correlation between motion and function. One class of biological machines is molecular motors in living cells, which directly convert chemical energy into mechanical work. They coexist in every eukaryotic cell, but differ in their types of motion, the filaments they bind to, the cargos they carry, as well as the work they perform. Such natural structures offer inspiration and blueprints for constructing DNA-assembled artificial systems, which mimic their functionality. In this article, we describe two g…
DNA supercoils are generated in genome regulation processes such as transcription and replication, and provide mechanical feedback to such processes. Under tension, DNA supercoil can present a coexistence state of plectonemic (P) and stretched (S) phases. Experiments have revealed the dynamic behaviors of plectoneme, e.g. diffusion, nucleation and hopping. To represent these dynamics with computational changes, we demonstrated first the fast dynamics on the DNA to reach torque equilibrium within the P and S phases, and then identified the two-phase boundaries as collective slow variables to de…
Cooperativity plays an important role in the action of proteins bound to DNA. A simple, mechanical mechanism for cooperativity, in the form of a tension-mediated interaction between proteins bound to DNA at two different locations is proposed. These proteins are not in direct physical contact. DNA segments intercalating bound proteins are modeled as a Worm-Like Chain, which is free to deform in two dimensions. The tension-controlled protein-protein interaction is the consequence of two effects produced by the protein binding. The first is the introduction of a bend in the host DNA and the seco…
