Diffusive dynamics of DNA unzipping in a nanopore

When an electric field is applied to an insulating membrane, movement of charged particles through a nanopore is induced. The measured ionic current reports on biomolecules passing through the nanopore. In this work, we explored the kinetics of DNA unzipping in a nanopore using our coarse‐grained model (Stachiewicz and Molski, J. Comput. Chem. 2015, 36, 947). Coarse graining allowed a more detailed analysis for a wider range of parameters than all‐atom simulations. Dependence of the translocation mode (unzipping or distortion) on the pore diameter was examined, and the threshold voltages were estimated. We determined the potential of mean force, position‐dependent diffusion coefficient, and position‐dependent effective charge for the DNA unzipping. The three molecular profiles were correlated with the ionic current and molecular events. On the unzipping/translocation force profile, two energy maxima were found, one of them corresponding to the unzipping, and the other to the translocation barriers. The unzipping kinetics were further explored using Brownian dynamics. © 2015 Wiley Periodicals, Inc.     

Statistics of polymer capture by a nanopore: A Brownian dynamics simulation study

We investigate the statistics of polymer capture by a nanopore using Brownian dynamics simulations. It is found that when the velocity flux is greater than a critical velocity flux, the capture picture is a random selection process, otherwise it tends to a statistical process governed by energetic considerations. In addition, the chain ends capture probability decreases as the chain length increases and satisfies a power-law scaling of P0(N)~N-0.8.     

Radial dependence of DNA translocation velocity in a solid-state nanopore

The physical features (such as size and charge) of a molecule transiting a nanopore whose cross-section area is only slightly larger than that of the molecule can be inferred from the measured ion-current through the pore. The transport of DNA molecules through nanopores has been extensively studied in the hope to enable low-cost and high-throughput DNA sequencing. However, the experimentally measured velocities of DNA translocation have a wide distribution, and this compromises the sequencing. In order to better understand the origin of the wide distribution, I have carried out molecular dynamics simulations to study the radial dependence of the translocation velocity. The results suggest a stick-slip type of motion of the dsDNA near the pore surface and a smooth translocation of the dsDNA near the pore center. The smooth dsDNA translocation (with a constant velocity) is governed by the zeta-potential of the pore surface which can be modified by adjusting the pH value and/or the ion concentration of the bulk electrolyte. This enables the mean translocation velocity of the dsDNA to be tuned and reduced. In addition, simulation results suggest that the smooth transport of dsDNA can be achieved by minimizing the dsDNA’s interaction with the pore, for example by chemical modification of its surface.     

Identification of nucleotides by measuring their current during DNA translocation through a nanopore

The electrical current through nucleotide junctions (guanine [G], cytosine [C], adenine [A], and thymine [T] bases sandwiched between Ag atoms) was calculated using the electron propagator theory (Keldysh–Green function formalism). The magnitudes of the calculated currents change in the following hierarchy: I _A > I _G > I _C > I _T. The difference in the current magnitudes implies the possibility of nucleotide identification by measuring the current they conduct during DNA translocation through a nanopore.     

Modeling dimerizations of transmembrane proteins using Brownian dynamics simulations

The dimerizations of membrane proteins, Outer Membrane Phospholipase A (OMPLA) and glycophorin A (GPA), have been simulated by an adapted Brownian Dynamics program. To mimic the membrane protein environment, we introduced a hybrid electrostatic potential map of membrane and water for electrostatic interaction calculations. We added a van der Waals potential term to the force field of the current version of the BD program to simulate the short-range interactions of the two monomers. We reduced the BD sampling space from three dimensions to two dimensions to improve the efficiency of BD simulations for membrane proteins. The OMPLA and GPA dimers predicted by our 2D-BD simulation and structural refinement is in good agreement with the experimental structures. The adapted 2D-BD method could be used for prediction of dimerization of other membrane proteins, such as G protein-coupled receptors, to help better understanding of the structures and functions of membrane proteins.     

Spatial blockage of ionic current for electrophoretic translocation of DNA through a graphene nanopore

Graphene nanopore has been promising the ultra‐high resolution for DNA sequencing due to the atomic thickness and excellent electronic properties of the graphene monolayer. The dynamical translocation phenomena and/or behaviors underneath the blocked ionic current, however, have not been well unveiled to date for the translocation of DNA electrophoretically through a graphene nanopore. In this report, the assessment on the sensitivity of ionic current to instantaneous statuses of DNA in a 2.4 nm graphene nanopore was carried out based on the all‐atom molecular dynamics simulations. By filtering out the thermal noise of ionic current, the instantaneous conformational variations of DNA in a graphene nanopore have been unveiled from the fluctuations of ionic current, because of the spatial blockage effect of DNA against ionic current. Interestingly, the neighborhood effect of DNA against ionic current was also observed within a distance of 1.5 nm nearby the graphene nanopore, suggesting the further precise control for DNA translocation through a graphene nanopore in gene sequencing. Moreover, the sensitivity of the blocked ionic current toward the instantaneous conformations of DNA in a graphene nanopore demonstrates the great potential of graphene nanopores in the dynamics analysis of single molecules.     

478—Theory of Brdička current and the dependence of the current on cobalt ion concentration

An equation of Brdi?ka current and its experimental verification are presented, in which Brdi?ka current is expressed by a function of the surface concentration of protein, the bulk concentration of cobalt ion and two parameters, n_ck_c and k_f/k_d, characterizing the protein-zero-valent cobalt complex which is to catalize the hydrogen evolution, where n_c is the total number of sites on which the complex can be formed in a protein molecule, and k_c and k_d are the (average) constants representing the intrinsic catalytic activity and the lifetime respectively, of the complex.     

Covalent modification of single glass conical nanopore channel with 6-carboxymethyl-chitosan for pH modulated ion current rectification

In this study, a novel covalent modification method of the single glass conical nanopore channel with amphoteric 6-carboxymethyl-chitosan (CMC) was designed to obtain a smart device responsive to a broad range of pH stimuli. This response is highly sensitive, reversible and reproducible. The CMC modified channel possessing carboxyl and amino groups was able to regulate ion transport selectivity and ion current rectification properties which depend on surface charges at various pH values. Each modification step was characterized by simply measuring the current–voltage (I–V) curves of the nanopore channel.     

Effect of internal viscosity on Brownian dynamics of DNA molecules in shear flow

The results of Brownian dynamics simulations of a single DNA molecule in shear flow are presented taking into account the effect of internal viscosity. The dissipative mechanism of internal viscosity is proved necessary in the research of DNA dynamics. A stochastic model is derived on the basis of the balance equation for forces acting on the chain. The Euler method is applied to the solution of the model. The extensions of DNA molecules for different Weissenberg numbers are analyzed. Comparison with the experimental results available in the literature is carried out to estimate the contribution of the effect of internal viscosity.     

Brownian dynamics simulations of electrophoretic DNA separations in a sparse ordered post array

We use Brownian dynamics simulations to analyze the electrophoretic separation of λ-DNA (48.5 kbp) and T4-DNA (169 kbp) in a hexagonal array of 1 μm diameter posts with a 3 μm center-to-center distance. The simulation method takes advantage of an efficient interpolation algorithm for the non-uniform electric field to reach an ensemble size (100 molecules) and simulation length scale (1 mm) that produces meaningful results for the average electrophoretic mobility and effective diffusion (dispersion) coefficient of these macromolecules as they move through the array. While the simulated electrophoretic mobility for λ-DNA is close to the experimental data, the simulation underestimates the magnitude of the corresponding dispersion coefficient. The simulations predict baseline resolution in a 15 mm device after 7 min using an electric field around 30 V/cm, with the resolution increasing exponentially as the electric field further decreases. The mobility and dispersivity data point out two essential phenomena that have been overlooked in previous models of DNA electrophoresis in post arrays: the relaxation time between collisions and simultaneous collisions with multiple posts.     

Web interface for Brownian dynamics simulation of ion transport and its applications to beta-barrel pores

Brownian dynamics (BD) based on accurate potential of mean force is an efficient and accurate method for simulating ion transport through wide ion channels. Here, a web-based graphical user interface (GUI) is presented for carrying out grand canonical Monte Carlo (GCMC) BD simulations of channel proteins: http://www.charmm-gui.org/input/gcmcbd. The webserver is designed to help users avoid most of the technical difficulties and issues encountered in setting up and simulating complex pore systems. GCMC/BD simulation results for three proteins, the voltage dependent anion channel (VDAC), α-Hemolysin (α-HL), and the protective antigen pore of the anthrax toxin (PA), are presented to illustrate the system setup, input preparation, and typical output (conductance, ion density profile, ion selectivity, and ion asymmetry). Two models for the input diffusion constants for potassium and chloride ions in the pore are compared: scaling of the bulk diffusion constants by 0.5, as deduced from previous all-atom molecular dynamics simulations of VDAC, and a hydrodynamics based model (HD) of diffusion through a tube. The HD model yields excellent agreement with experimental conductances for VDAC and α-HL, while scaling bulk diffusion constants by 0.5 leads to underestimates of 10-20%. For PA, simulated ion conduction values overestimate experimental values by a factor of 1.5-7 (depending on His protonation state and the transmembrane potential), implying that the currently available computational model of this protein requires further structural refinement.     

Brownian dynamics simulations of single-wall carbon nanotube separation by type using dielectrophoresis

We theoretically investigate the separation of individualized metallic and semiconducting single-wall carbon nanotubes (SWNTs) in a dielectrophoretic (DEP) flow device. The SWNT motion is simulated by a Brownian dynamics (BD) algorithm, which includes the translational and rotational effects of hydrodynamic, Brownian, dielectrophoretic, and electrophoretic forces. The device geometry is chosen to be a coaxial cylinder because it yields effective flow throughput, the DEP and flow fields are orthogonal to each other, and all the fields can be described analytically everywhere. We construct a flow-DEP phase map showing different regimes, depending on the relative magnitudes of the forces in play. The BD code is combined with an optimization algorithm that searches for the conditions that maximize the separation performance. The optimization results show that a 99% sorting performance can be achieved with typical SWNT parameters by operating in a region of the phase map where the metallic SWNTs completely orient with the field, whereas the semiconducting SWNTs partially flow-align.     

Elastic coefficient of a single polymer chain by using Brownian dynamics analysis

The elastic coefficient of a single polystyrene chain has been experimentally evaluated by using Brownian dynamics analysis. The Brownian motion of the chain is probed using a particle trapped by optical tweezers with a negligibly small spring constant. The displacement of the particle due to Brownian motion is measured by an interferometer assembled using the same laser beam as the optical tweezers. Two methods are employed for Brownian dynamics analysis: (1) the analysis of the time course of the displacement of the particle and (2) the fitting of the power spectrum of Brownian motion with a Lorentzian. The elastic constant of a polystyrene chain in dichloromethane at 21 degrees C is estimated to be 6.4 x 10(-6) and 1.1 x 10(-5) N/m when methods (1) and (2) are employed, respectively. The elastic constant obtained by approximating the polystyrene chain to a freely jointed chain is in agreement with the experimentally evaluated elastic constant.     

Electric-field-controlled water and ion permeation of a hydrophobic nanopore

The permeation of hydrophobic, cylindrical nanopores by water molecules and ions is investigated under equilibrium and out-of-equilibrium conditions by extensive molecular-dynamics simulations. Neglecting the chemical structure of the confining pore surface, we focus on the effects of pore radius and electric field on permeation. The simulations confirm the intermittent filling of the pore by water, reported earlier under equilibrium conditions for pore radii larger than a critical radius R(c). Below this radius, water can still permeate the pore under the action of a strong electric field generated by an ion concentration imbalance at both ends of the pore embedded in a structureless membrane. The water driven into the channel undergoes considerable electrostriction characterized by a mean density up to twice the bulk density and by a dramatic drop in dielectric permittivity which can be traced back to a considerable distortion of the hydrogen-bond network inside the pore. The free-energy barrier to ion permeation is estimated by a variant of umbrella sampling for Na(+), K(+), Ca(2+), and Cl(-) ions, and correlates well with known solvation free energies in bulk water. Starting from an initial imbalance in ion concentration, equilibrium is gradually restored by successive ion passages through the water-filled pore. At each passage the electric field across the pore drops, reducing the initial electrostriction, until the pore, of radius less than R(c), closes to water and hence to ion transport, thus providing a possible mechanism for voltage-dependent gating of hydrophobic pores.     

Modulating ion current rectification generating high energy output in a single glass conical nanopore channel by concentration gradient

Inspired by biological systems that have the inherent skill to generate considerable bioelectricity from the salt content in fluids with highly selective ion channels and pumps on cell membranes,herein,a fully abiotic,single glass conical nanopores energy-harvesting is demonstrated.Ion current rectification(ICR)in negatively charged glass conical nanopores is shown to be controlled by the electrolyte concentration gradient depending on the direction of ion diffusion.The degree of ICR is enhanced with the increasing forward concentration difference.An unusual rectification inversion is observed when the concentration gradient is reversely applied.The maximum power output with the individual nanopore approaches10~4pW.This facile and cost-efficient energy-harvesting system has the potential to power tiny biomedical devices or construct future clean-energy recovery plants.     

The mechanism of the self-assembly of associating DNA molecules under shear flow: Brownian dynamics simulation

A shear flow induces the assembly of DNAs with the sticky spots. In order to strictly interpret the mechanism of shear-induced DNA assembly, Brownian dynamics simulations with the bead-spring model were carried out for these molecules at various ranges of the Weissenberg numbers (We). We calculate a formation time and analyze the radial distribution function of end beads and the probability distribution of fractional extension at the formation time to understand the mechanism of shear-induced assembly. At low Weissenberg number the formation time, which is defined as an elapsed time until a multimer forms for the first time, decreases rapidly, reaching a plateau at We = 1000. A shear flow changes the radial distribution of end beads, which is almost the same regardless of the Weissenberg number. A shear flow deforms and stretches the molecules and generates different distributions between end beads with a stickly spot. The fractional extension progresses rapidly in shear flow from a Gaussian-like distribution to a uniform distribution. The progress of the distribution of fractional extension increases the possibility of meeting of end beads. In shear flow, the inducement of the assembly mainly results from the progress of the probability distribution of fractional extension. We also calculate properties such as the radius of gyration, stretch, and so on. As the Weissenberg number increases, the radius of gyration at the formation time also increases rapidly, reaching a plateau at We = 1000.     

Brownian dynamics of mixed surfactant micelles

We investigate micelle formation in a system containing two or more different amphiphiles with different geometries using a stochastic molecular-dynamics (MD) simulation method. For a binary system containing two amphiphiles, we calculate the critical micelle concentration (CMC) and cluster distribution for the mixture at several mole fractions and compare the simulation results with those predicted by analytic theories in the dilute limit and with experiments. We find that the CMC obtained from molecular mean-field theory agrees well with our simulation results. Motivated by the industrial use of mixed surfactant systems, we then extend our studies to a system containing six different chain lengths drawn from a Poisson distribution. We find that unlike a binary mixture of amphiphiles, the different species cancel the effects of each other so that the cluster distribution for the mixture has a shape of a system consisted entirely of amphiphiles of length equal to the mean chain length of the Poisson distribution.