Molecular Dynamics Simulation of Multivalent-Ion Mediated Attraction between DNA Molecules

Department of Physics, National University of Singapore, 2 Science Drive 3, Singapore 117542.
Physical Review Letters (Impact Factor: 7.51). 03/2008; 100(11):118301. DOI: 10.1103/PhysRevLett.100.118301
Source: PubMed


All atom molecular dynamics simulations with explicit water were done to study the interaction between two parallel double-stranded DNA molecules in the presence of the multivalent counterions putrescine (2+), spermidine (3+), spermine (4+) and cobalt hexamine (3+). The inter-DNA interaction potential is obtained with the umbrella sampling technique. The attractive force is rationalized in terms of the formation of ion bridges, i.e., multivalent ions which are simultaneously bound to the two opposing DNA molecules. The lifetime of the ion bridges is short on the order of a few nanoseconds.

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Available from: Johan R C van der Maarel, Dec 15, 2012
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    • "Therefore, the assumption that Ncrit = 0.88 – 0.90 has to be based on the wide range of experimental observations that have documented this behavior and remains an empirical relation. In order to understand the origin of the attractive interactions that lead to condensation, when this critical degree of DNA charge neutralization has been met by the addition of oligocations, theoretical models beyond mean field theories must be applied (14,32,69). "
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    ABSTRACT: We report a systematic study of the condensation of plasmid DNA by oligocations with variation of the charge, Z, from +3 to +31. The oligocations include a series of synthetic linear ε-oligo(L-lysines), (denoted εKn, n = 3–10, 31; n is the number of lysines with the ligand charge Z = n+1) and branched α-substituted homologues of εK10: εYK10, εLK10 (Z = +11); εRK10, εYRK10 and εLYRK10 (Z = +21). Data were obtained by light scattering, UV absorption monitored precipitation assay and isothermal titration calorimetry in a wide range concentrations of DNA and monovalent salt (KCl, CKCl). The dependence of EC50 (ligand concentration at the midpoint of DNA condensation) on C(KCl) shows the existence of a salt-independent regime at low C(KCl) and a salt-dependent regime with a steep rise of EC50 with increase of C(KCl). Increase of the ligand charge shifts the transition from the salt-independent to salt-dependent regime to higher C(KCl). A novel and simple relationship describing the EC50 dependence on DNA concentration, charge of the ligand and the salt-dependent dissociation constant of the ligand–DNA complex is derived. For the ε-oligolysines εK6–εK10, the experimental dependencies of EC50 on C(KCl) and Z are well-described by an equation with a common set of parameters. Implications from our findings for understanding DNA condensation in chromatin are discussed.
    Full-text · Article · Mar 2012 · Nucleic Acids Research
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    • "The available experimental data are mostly quantitative, not accurate enough to be used for validating numerical models. In addition, modelling of microbiological processes involves complex molecular interactions difficult for direct modelling due to prohibitive number of molecules involved and time scales far beyond those available for simulation methods at molecular level (compare Kreuzer and Grunze, 2001 or Dai et al., 2008). Hence, despite great progress in recent modelling of single DNA molecules in flow (e.g. "
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    ABSTRACT: In this paper we aim to create an experimental and numerical model of nano and micro filaments suspended in a confined Poiseuille flow. The experimental data obtained for short nanofibres will help to elucidate fundamental questions concerning mobility and deformation of biological macromolecules due to hydrodynamic stresses from the surrounding fluid motion. Nanofibres used in the experiments are obtained by electrospinning polymer solutions. Their typical dimensions are 100–1000 μm (length) and 0.1–1 μm (diameter). The nanofibre dynamics is followed experimentally under a fluorescence microscope. A precise multipole expansion method of solving the Stokes equations, and its numerical implementation are used to construct a bead-spring model of a filament moving in a Poiseuille flow between two infinite parallel walls. Simulations show typical behaviour of elongated macromolecules. Depending on the parameters, folding and unfolding sequences of a flexible filament are observed, or a rotational and translation motion of a shape-preserving filament. An important result of our experiments is that nanofibres do not significantly change their shape while interacting with a micro-flow. It appeared that their rotational motion is better reproduced by the shape-preserving Stokesian bead model with all pairs of beads connected by springs, omitting explicit bending forces.
    Full-text · Article · Dec 2010 · International Journal of Heat and Fluid Flow
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    • "Recent theoretical studies have shown that multivalent ions can stabilize DNA–DNA interactions at an inter-helical distance (24–37 Å) that does not allow direct intermolecular contacts (52–55). At this distance range the minimum energy configuration corresponds to a parallel alignment of the duplexes. "
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    ABSTRACT: The assembly of DNA duplexes into higher-order structures plays a major role in many vital cellular functions such as recombination, chromatin packaging and gene regulation. However, little is currently known about the molecular structure and stability of direct DNA-DNA interactions that are required for such functions. In nature, DNA helices minimize electrostatic repulsion between double helices in several ways. Within crystals, B-DNA forms either right-handed crossovers by groove-backbone interaction or left-handed crossovers by groove-groove juxtaposition. We evaluated the stability of such crossovers at various ionic concentrations using large-scale atomistic molecular dynamics simulations. Our results show that right-handed DNA crossovers are thermodynamically stable in solution in the presence of divalent cations. Attractive forces at short-range stabilize such crossover structures with inter-axial separation of helices less than 20 A. Right-handed crossovers, however, dissociate swiftly in the presence of monovalent ions only. Surprisingly, left-handed crossovers, assembled by sequence-independent juxtaposition of the helices, appear unstable even at the highest concentration of Mg(2+)studied here. Our study provides new molecular insights into chiral association of DNA duplexes and highlights the unique role divalent cations play in differential stabilization of crossover structures. These results may serve as a rational basis to understand the role DNA crossovers play in biological processes.
    Full-text · Article · Mar 2010 · Nucleic Acids Research
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