DNA Confinement drives uncoating of the HIV Virus

We present a model for the uncoating of the HIV virus driven by forces exerted on the protein shell of HIV generated by DNA confinement

Reentrant Condensation of DNA induced by Multivalent Counterions

A theory of condensation and resolubilization of a dilute DNA solution with growing concentration of multivalent cations, N is suggested. It is based on a new theory of screening of a macroion by multivalent cations, which shows that due to strong cation correlations at the surface of DNA the net charge of DNA changes sign at some small concentration of cations N_0. DNA condensation takes place in the vicinity of N_0, where absolute value of the DNA net charge is small and the correlation induced short range attraction dominates the Coulomb repulsion. At N > N_0 positive DNA should move in the oppisite direction in an electrophoresis experiment. From comparison of our theory with experimental values of condensation and resolubilization thresholds for DNA solution containing Spe$^{4+}$, we obtain that N_0 = 3.2 mM and that the energy of DNA condensation per nucleotide is $0.07 k_B T$.Comment: 8 pages, 4 figures, references correcte

Competition between condensation of monovalent and multivalent ions in DNA aggregation

We discuss the distribution of ions around highly charged PEs when there is competition between monovalent and multivalent ions, pointing out that in this case the number of condensed ions is sensitive to short-range interactions, salt, and model-dependent approximations. This sensitivity is discussed in the context of recent experiments on DNA aggregation, induced by multivalent counterions such as spermine and spermidine.Comment: 6 pages, 1 figur

Effects of mechanical strain on thermal denaturation of DNA

As sections of a strand duplexed DNA denature when exposed to high temperature, the excess linking number is taken up by the undenatured portions of the molecule. The mechanical energy that arises because of the overwinding of the undenatured sections can, in principle, alter the nature of the thermal denaturation process. Assuming that the strains associated with this overwinding are not relieved, we find that a simple model of strain-altered melting leads to a suppression of the melting transition when the unaltered transition is continuous. When the melting transition is first order in the absence of strain associated with overwinding, the modification is to a third order phase transition.Comment: 4 pages, 5 figures, RevTe

Unzipping Kinetics of Double-Stranded DNA in a Nanopore

We studied the unzipping kinetics of single molecules of double-stranded DNA by pulling one of their two strands through a narrow protein pore. PCR analysis yielded the first direct proof of DNA unzipping in such a system. The time to unzip each molecule was inferred from the ionic current signature of DNA traversal. The distribution of times to unzip under various experimental conditions fit a simple kinetic model. Using this model, we estimated the enthalpy barriers to unzipping and the effective charge of a nucleotide in the pore, which was considerably smaller than previously assumed.Comment: 10 pages, 5 figures, Accepted: Physics Review Letter

Screening of a macroion by multivalent ions: A new boundary condition for Poisson-Boltzmann equation and charge inversion

Screening of a macroion by multivalent counterions is considered. It is shown that ions form strongly correlated liquid at the macroion surface. Cohesive energy of this liquid leads to strong additional attraction of counterions to the surface. Away from the surface this attraction is taken into account by a new boundary condition for the Poisson-Boltzmann equation. This equation is solved with the new boundary condition for a charged flat surface and a long cylinder. For a cylinder Onsager-Manning theory looses its universality so that apparent charge of the cylinder is smaller than their theory predicts and depends on its bare charge. It can also vanish or change sign.Comment: 4 pages, no figure

The pulling force of a single DNA molecule condensed by spermidine

In a recent experiment, a single DNA double helix is stretched and relaxed in the presence of spermidine, a short positive polyelectrolyte, and the pulling force is measured as a function of DNA extension. In a certain range of spermidine concentration, a force plateau appears whose value shows maximum as a function of spermidine concentration. We present a quantitative theory of this plateau force based on the theory of reentrant condensation and derive almost parabolic behavior of the plateau force as a function of the logarithm of the spermidine concentration in the range of condensation. Our result is in good agreement with experimental data.Comment: 4 pages, 4 figures. Small change in the text, no change in result

The bend stiffness of S-DNA

We formulate and solve a two-state model for the elasticity of nicked, double-stranded DNA that borrows features from both the Worm Like Chain and the Bragg--Zimm model. Our model is computationally simple, and gives an excellent fit to recent experimental data through the entire overstretching transition. The fit gives the first value for the bending stiffness of the overstretched state as about 10 nm*kbt, a value quite different from either B-form or single-stranded DNA.Comment: 7 pages, 1 figur

Electrostatic image effects for counter-ions between charged planar walls

We study the effect of dielectric inhomogeneities on the interaction between two planparallel charged surfaces with oppositely charged mobile charges in between. The dielectric constant between the surfaces is assumed to be different from the dielectric constant of the two semiinfinite regions bounded by the surfaces, giving rise to electrostatic image interactions. We show that on the weak coupling level the image charge effects are generally small, making their mark only in the second order fluctuation term. However, in the strong coupling limit, the image effects are large and fundamental. They modify the interactions between the two surfaces in an essential way. Our calculations are particularly useful in the regime of parameters where computer simulations would be difficult and extremely time consuming due to the complicated nature of the long range image potentials.Comment: 21 pages, 8 figure

Mechanisms of Small Molecule-DNA Interactions Probed by Single-molecule Force Spectroscopy

There is a wide range of applications for non-covalent DNA binding ligands, and optimization of such interactions requires detailed understanding of the binding mechanisms. One important class of these ligands is that of intercalators, which bind DNA by inserting aromatic moieties between adjacent DNA base pairs. Characterizing the dynamic and equilibrium aspects of DNA-intercalator complex assembly may allow optimization of DNA binding for specific functions. Single-molecule force spectroscopy studies have recently revealed new details about the molecular mechanisms governing DNA intercalation. These studies can provide the binding kinetics and affinity as well as determining the magnitude of the double helix structural deformations during the dynamic assembly of DNA–ligand complexes. These results may in turn guide the rational design of intercalators synthesized for DNA-targeted drugs, optical probes, or integrated biological self-assembly processes. Herein, we survey the progress in experimental methods as well as the corresponding analysis framework for understanding single molecule DNA binding mechanisms. We discuss briefly minor and major groove binding ligands, and then focus on intercalators, which have been probed extensively with these methods. Conventional mono-intercalators and bis-intercalators are discussed, followed by unconventional DNA intercalation. We then consider the prospects for using these methods in optimizing conventional and unconventional DNA-intercalating small molecules