DNA Barcodes Using a Dual Nanopore Device.

We report a novel method based on the current blockade (CB) characteristics obtained from a dual nanopore device that can determine DNA barcodes with near-perfect accuracy using a Brownian dynamics simulation strategy. The method supersedes our previously reported velocity correction algorithm (S. Seth and A.

Fine structures of intrinsically disordered proteins.

We report simulation studies of 33 single intrinsically disordered proteins (IDPs) using coarse-grained bead-spring models where interactions among different amino acids are introduced through a hydropathy matrix and additional screened Coulomb interaction for the charged amino acid beads. Our simulation studies of two different hydropathy scales (HPS1, HPS2) [Dignon et al., PLoS Comput.

Universality in conformations and transverse fluctuations of a semi-flexible polymer in a crowded environment.

We study the universal aspects of polymer conformations and transverse fluctuations for a single swollen chain characterized by a contour length L and a persistence length ℓp in two dimensions (2D) and three dimensions (3D) in the bulk, as well as in the presence of excluded volume (EV) particles of different sizes occupying different area/volume fractions. In the absence of the EV particles, we extend the previously established universal scaling relations in 2D [Huang et al., J.

Discriminating protein tags on a dsDNA construct using a Dual Nanopore Device.

We report Brownian dynamics simulation results with the specific goal to identify key parameters controlling the experimentally measurable characteristics of protein tags on a dsDNA construct translocating through a double nanopore setup. First, we validate the simulation scheme in silico by reproducing and explaining the physical origin of the asymmetric experimental dwell time distributions of the oligonucleotide flap markers on a 48 kbp long dsDNA at the left and the right pore. We study the effect of the electric field inside and beyond the pores, critical to discriminate the protein tags based on their effective charges and masses revealed through a generic power-law dependence of the average dwell time at each pore.

How capture affects polymer translocation in a solitary nanopore.

DNA capture with high fidelity is an essential part of nanopore translocation. We report several important aspects of the capture process and subsequent translocation of a model DNA polymer through a solid-state nanopore in the presence of an extended electric field using the Brownian dynamics simulation that enables us to record statistics of the conformations at every stage of the translocation process. By releasing the equilibrated DNAs from different equipotentials, we observe that the capture time distribution depends on the initial starting point and follows a Poisson process.

DNA barcode by flossing through a cylindrical nanopore.

We report an accurate method to determine DNA barcodes from the dwell time measurement of protein tags (barcodes) along the DNA backbone using Brownian dynamics simulation of a model DNA and use a recursive theoretical scheme which improves the measurements to almost 100% accuracy. The heavier protein tags along the DNA backbone introduce a large speed variation in the chain that can be understood using the idea of non-equilibrium tension propagation theory. However, from an initial rough characterization of velocities into "fast" (nucleotides) and "slow" (protein tags) domains, we introduce a physically motivated interpolation scheme that enables us to determine the barcode velocities rather accurately.

DNA barcodes using a double nanopore system.

The potential of a double nanopore system to determine DNA barcodes has been demonstrated experimentally. By carrying out Brownian dynamics simulation on a coarse-grained model DNA with protein tag (barcodes) at known locations along the chain backbone, we demonstrate that due to large variation of velocities of the chain segments between the tags, it is inevitable to under/overestimate the genetic lengths from the experimental current blockade and time of flight data. We demonstrate that it is the tension propagation along the chain's backbone that governs the motion of the entire chain and is the key element to explain the non uniformity and disparate velocities of the tags and DNA monomers under translocation that introduce errors in measurement of the length segments between protein tags.

Polymer escape through a three dimensional double-nanopore system.

We study the escape dynamics of a double-stranded DNA (dsDNA) through an idealized double nanopore geometry subject to two equal and opposite forces (tug-of-war) using Brownian dynamics (BD) simulation. In addition to the geometrical restrictions imposed on the cocaptured dsDNA segment in between the pores, the presence of tug-of-war forces at each pore results in a variation of the local chain stiffness for the segment of the chain in between the pores, which increases the overall stiffness of the chain. We use the BD simulation results to understand how the intrinsic chain stiffness and the tug-of-war forces affect the escape dynamics by monitoring the local chain persistence length ℓ, the residence time of the individual monomers W(m) in the nanopores, and the chain length dependence of the escape time ⟨τ⟩ and its distribution.

Tug of war in a double-nanopore system.

We simulate a tug-of-war (TOW) scenario for a model double-stranded DNA threading through a double nanopore (DNP) system. The DNA, simultaneously captured at both pores, is subject to two equal and opposite forces -f[over ⃗]_{L}=f[over ⃗]_{R} (TOW), where f[over ⃗]_{L} and f[over ⃗]_{R} are the forces applied to the left and the right pore, respectively. Even though the net force on the DNA polymer Δf[over ⃗]_{LR}=f[over ⃗]_{L}+f[over ⃗]_{R}=0, the mean first passage time (MFPT) 〈τ〉 depends on the magnitude of the TOW forces |f_{L}|=|f_{R}|=f_{LR}.