Showing papers on "Molecular models of DNA published in 2018"

Dynamics of supercoiled DNA with complex knots: large-scale rearrangements and persistent multi-strand interlocking.

Abstract: Knots and supercoiling are both introduced in bacterial plasmids by catalytic processes involving DNA strand passages. While the effects on plasmid organization has been extensively studied for knotting and supercoiling taken separately, much less is known about their concurrent action. Here, we use molecular dynamics simulations and oxDNA, an accurate mesoscopic DNA model, to study the kinetic and metric changes introduced by complex (five-crossing) knots and supercoiling in 2 kbp-long DNA rings. We find several unexpected results. First, the conformational ensemble is dominated by two distinct states, differing in branchedness and knot size. Secondly, fluctuations between these states are as fast as the metric relaxation of unknotted rings. In spite of this, certain boundaries of knotted and plectonemically-wound regions can persist over much longer timescales. These pinned regions involve multiple strands that are interlocked by the cooperative action of topological and supercoiling constraints. Their long-lived character may be relevant for the simplifying action of topoisomerases.

Dynamics of supercoiled DNA with complex knots: large-scale rearrangements and persistent multi-strand interlocking

Abstract: Knots and supercoiling are both introduced in bacterial plasmids by catalytic processes involving DNA strand passages. While the effects on plasmid organization has been extensively studied for knotting and supercoiling taken separately, much less is known about their concurrent action. Here, we use molecular dynamics simulations and oxDNA, an accurate mesoscopic DNA model, to study the kinetic and metric changes introduced by complex (five-crossing) knots and supercoiling in 2kbp-long DNA rings. We find several unexpected results. First, the conformational ensemble is dominated by two distinct states, differing in branchedness and knot size. Secondly, fluctuations between these states are as fast as the metric relaxation of unknotted rings. In spite of this, certain boundaries of knotted and plectonemically-wound regions can persist over much longer timescales. These pinned regions involve multiple strands that are interlocked by the cooperative action of topological and supercoiling constraints. Their long-lived character may be relevant for the simplifying action of topoisomerases.

Coupled Sine-Gordon Systems in DNA Dynamics

Abstract: We consider a model called the coupled sine-Gordon equation for DNA dynamics by introducing two double helix structures. The second double helix structure is unilaterally influenced by the first one. The completely integrable coupled sine-Gordon equation admits kink-antikink solitons with increased width representing a wide base pair opening configuration in DNA. Also we propose another coupled sine-Gordon model with variable coefficients for DNA dynamics under an inhomogeneous background. We find that the inhomogeneous DNA model has many interesting localized nonrational rogue wave solutions. We can find that the appearance of the rogue waves (possibly means the genetic mutation) in the nonlinear DNA model is highly related to the inhomogeneity.

An Accurate Estimate of the Free Energy and Phase Diagram of All-DNA Bulk Fluids.

Abstract: We present a numerical study in which large-scale bulk simulations of self-assembled DNA constructs have been carried out with a realistic coarse-grained model. The investigation aims at obtaining a precise, albeit numerically demanding, estimate of the free energy for such systems. We then, in turn, use these accurate results to validate a recently proposed theoretical approach that builds on a liquid-state theory, the Wertheim theory, to compute the phase diagram of all-DNA fluids. This hybrid theoretical/numerical approach, based on the lowest-order virial expansion and on a nearest-neighbor DNA model, can provide, in an undemanding way, a parameter-free thermodynamic description of DNA associating fluids that is in semi-quantitative agreement with experiments. We show that the predictions of the scheme are as accurate as those obtained with more sophisticated methods. We also demonstrate the flexibility of the approach by incorporating non-trivial additional contributions that go beyond the nearest-neighbor model to compute the DNA hybridization free energy.

Charge transport in a DNA model with solvent interaction

Abstract: The charge transport in the modified DNA model is studied by taking into account the factor of solvent and the effect of coupling motions of nucleotides. We report on the presence of the modulational instability (MI) of a plane wave for charge migration in DNA and the generation of soliton-like excitations in DNA nucleotides. By applying the continuum approximation, we show that the original differential-difference equation for the DNA dynamics can be reduced to a set of three coupled nonlinear equations. The linear stability analysis of wave solutions of the coupled systems is performed and the growth rate of instability is found numerically. We also investigate the impact of solvent interaction. The solvent factor introduces a new behavior to the wave patterns, modifying also the intrinsic properties of localized structures. In the numerical simulations, we show that the solitons exists when taking into account the effect of solvent and confirms an highest propagation of localized structures in the systems. The effect of solvent forces introduces a robustness behavior to the formed patterns, reinforcing the idea that the information in the DNA model is confined and concentrated to specific regions for efficiency. We also show that the localized structures can be disappeared with the highest value of solvent factor and thereafter the information within the molecule is not perceptible or not transmitted to another sites.

An Accurate Estimate of the Free Energy and Phase Diagram of All-DNA Bulk Fluids

Abstract: We present a numerical study in which large-scale bulk simulations of self-assembled DNA constructs have been carried out with a realistic coarse-grained model. The investigation aims at obtaining a precise, albeit numerically demanding, estimate of the free energy for such systems. We then, in turn, use these accurate results to validate a recently proposed theoretical approach that builds on a liquid-state theory, the Wertheim theory, to compute the phase diagram of all-DNA fluids. This hybrid theoretical/numerical approach, based on the lowest-order virial expansion and on a nearest-neighbor DNA model, can provide, in an undemanding way, a parameter-free thermodynamic description of DNA associating fluids that is in semi-quantitative agreement with experiments. We show that the predictions of the scheme are as accurate as those obtained with more sophisticated methods. We also demonstrate the flexibility of the approach by incorporating non-trivial additional contributions that go beyond the nearest-neighbor model to compute the DNA hybridization free energy.

Hierarchical multiscale simulation of DNA condensation

Abstract: DNA condensation at mesoscale level, induced by multivalent ions is of substantial importance for packing of DNA in vivo with many applications in biology, biotechnology and polymer physics. Rigorous modeling of this process with all-atom molecular dynamics (MD) simulations is presently impossible due to size and time scale limitations. Here, we present a hierarchical approach for systematic multiscale coarse-grained (CG) simulations of DNA condensation induced by the three-valent cobalt(III)-hexammine (CoHex3+). On the basis of all-atom MD simulations, we extract solvent-mediated effective potentials for a CG model of DNA and simulate DNA aggregation in the presence of CoHex3+. Further coarse-graining to a super-CG DNA model enables simulations of DNA condensation at mesoscale level. Modeling a 10 kbp-long DNA molecule results in formation of a toroid with distinct hexagonal packing in agreement with Cryo-EM observations. The approach uses no adjustable parameters and is applied on DNA up to megabase dimensions. It may be generalized to modeling chromatin up to chromosome size.

Investigation of DNA denaturation from generalized Morse potential

Abstract: In this paper, we present a non-linear model for DNA denaturation. We assume that the double-strands DNA interact via a realistic generalized Morse potential that reproduces well the features of the real interaction, as well as the used DNA model and that of Peyrard and Bishop. Using the Transfer Matrix Method , based on the resolution of a Schrodinger equation, we first determine exactly their solution, which are found to be bound states . Second, from an exact expression of the ground state, we compute the denaturation temperature and the free energy density, in terms of the potential parameters. Then, we calculate the contact probability, which is the probability to find the double-strands at a (finite) distance apart. The main conclusion is that, the present analytical study reveals that the generalized Morse potential is a good candidate for the study of DNA denaturation.