Modeling of polynucleotide translocation through protein pores and nanotubes

Kong, C. Y.; Muthukumar, Murugappan

doi:10.1002/1522-2683(200208)23:16<2697::aid-elps2697>3.0.co;2-m

Cited by 91 publications

(77 citation statements)

References 21 publications

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“…We have used the side-chain incorporated model to represent a single-stranded polynucleotide (20), because of its simplicity, fast computational speed, and past success. Each nucleotide is made up of three subunits (phosphate, sugar, and base), and each subunit is taken as a bead.…”

Section: Simulation Methodsmentioning

confidence: 99%

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Simulation of polymer translocation through protein channels

Muthukumar

Kong

2006

Proc. Natl. Acad. Sci. U.S.A.

128

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A modeling algorithm is presented to compute simultaneously polymer conformations and ionic current, as single polymer molecules undergo translocation through protein channels. The method is based on a combination of Langevin dynamics for coarse-grained models of polymers and the Poisson-Nernst-Planck formalism for ionic current. For the illustrative example of ssDNA passing through the ␣-hemolysin pore, vivid details of conformational fluctuations of the polymer inside the vestibule and ␤-barrel compartments of the protein pore, and their consequent effects on the translocation time and extent of blocked ionic current are presented. In addition to yielding insights into several experimentally reported puzzles, our simulations offer experimental strategies to sequence polymers more efficiently.T ranslocation of polymers through biological channels is very complex involving many machineries and is a fundamental step in many life processes. Although several essential features of translocation are richly documented in systems such as mRNP complex through nuclear pores (1-3), a simple system has only recently been identified for following the single-file passage of one isolated polymer through one channel (4-11). In this system, the channel is constituted by self-assembling heptamers of the Staphylococcus aureus ␣-hemolysin (␣HL) protein. The channel is assembled in a phospholipid bilayer, which offers a physical barrier, and the channel has an opening diameter of Ϸ1.4 nm at the narrowest constriction (12). A single-stranded polynucleotide, such as poly(deoxyadenylate) and poly(deoxycytidylate), is pulled through the channel by an externally applied voltage gradient across the channel in a solution of a strong electrolyte. The idea is that the ionic current through the channel caused by the passage of small ions of the electrolyte is blocked to a certain extent during the event of translocation of the polymer. It has been hoped that the extent and duration of the current blockade are unique signatures of the identity of the polymer, both in terms of the polymer's chemical characteristics and physical length.Even this simplest setup, where identical molecules undergo translocation, has generated several puzzling results. The distribution, P( ), of the duration of blockade of ionic current I b is very broad and appears to exhibit at least two peaks. In addition, there are several levels of ionic current blockade I b for the same molecule. It is standard practice in experimental investigations to combine the histograms of and I b (8). The resultant scatter plots always yield two groups of data even for monodisperse homopolymers.To gain insight into these puzzles, we have developed the following simulation. It is complementary to a flurry of theoretical activity (13-21), based on entropic barrier dynamics (22), all of which lead to a generic P( ) unlike in experiments. Although it is indeed desirable to perform the computation ab initio, the size of the system to be simulated is forbiddingly large to enable such a compu...

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Section: Simulation Methodsmentioning

confidence: 99%

“…It is complementary to a flurry of theoretical activity (13)(14)(15)(16)(17)(18)(19)(20)(21), based on entropic barrier dynamics (22), all of which lead to a generic P( ) unlike in experiments. Although it is indeed desirable to perform the computation ab initio, the size of the system to be simulated is forbiddingly large to enable such a computation.…”

mentioning

confidence: 99%

Simulation of polymer translocation through protein channels

Muthukumar

Kong

2006

Proc. Natl. Acad. Sci. U.S.A.

128

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“…Theoretical models and Monte-Carlo simulations that describe the transport of polynucleotides and idealized polymers through idealized nanoscale pores have been developed. [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] In addition, the ability of another ion channel to catalyze DNA transport has been identified by Szabo and colleagues. 56 The rate at which polynucleotides enter the ␣HL channel is voltage dependent.…”

Section: Introductionmentioning

confidence: 99%

Probing single nanometer-scale pores with polymeric molecular rulers

Henrickson¹,

DiMarzio

Wang³

et al. 2010

The Journal of Chemical Physics

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We previously demonstrated that individual molecules of single-stranded DNA can be driven electrophoretically through a single Staphylococcus aureus ␣-hemolysin ion channel. Polynucleotides thread through the channel as extended chains and the polymer-induced ionic current blockades exhibit stable modes during the interactions. We show here that polynucleotides can be used to probe structural features of the ␣-hemolysin channel itself. Specifically, both the pore length and channel aperture profile can be estimated. The results are consistent with the channel crystal structure and suggest that polymer-based "molecular rulers" may prove useful in deducing the structures of nanometer-scale pores in general.

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“…Accordingly, the polymer translocation has attracted a considerable number of experimental, [7][8][9][10][11][12][13][14] theoretical, [15][16][17][18][19][20][21][22][23][24][25][26][27][28] and numerical studies. [29][30][31][32][33][34][35][36] The translocation of a polymer through a nanopore faces a large entropic barrier due to the loss of a great number of available configurations. In order to overcome the barrier and to speed up the translocation, an external field or interaction is often introduced.…”

Section: Introductionmentioning

confidence: 99%

Polymer translocation through a nanopore: A two-dimensional Monte Carlo study

Luo

Ala-Nissilä

Ying

2006

The Journal of Chemical Physics

119

144

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Polymer translocation through a nanopore induced by adsorption: Monte Carlo simulation of a coarse-grained model J. Chem. Phys. 121, 6042 (2004); 10.1063/1.1785776 This article is copyrighted as indicated in the article. Reuse of AIP content is subject to the terms at: http://scitation. We investigate the problem of polymer translocation through a nanopore in the absence of an external driving force. To this end, we use the two-dimensional fluctuating bond model with single-segment Monte Carlo moves. To overcome the entropic barrier without artificial restrictions, we consider a polymer which is initially placed in the middle of the pore and study the escape time required for the polymer to completely exit the pore on either end. We find numerically that scales with the chain length N as ϳ N 1+2 , where is the Flory exponent. This is the same scaling as predicted for the translocation time of a polymer which passes through the nanopore in one direction only. We examine the interplay between the pore length L and the radius of gyration R g . For L Ӷ R g , we numerically verify that asymptotically ϳ N 1+2 . For L ӷ R g , we find ϳ N. In addition, we numerically find the scaling function describing crossover between short and long pores. We also show that has a minimum as a function of L for longer chains when the radius of gyration along the pore direction R ʈ Ϸ L. Finally, we demonstrate that the stiffness of the polymer does not change the scaling behavior of translocation dynamics for single-segment dynamics.

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Modeling of polynucleotide translocation through protein pores and nanotubes

Cited by 91 publications

References 21 publications

Simulation of polymer translocation through protein channels

Simulation of polymer translocation through protein channels

Probing single nanometer-scale pores with polymeric molecular rulers

Polymer translocation through a nanopore: A two-dimensional Monte Carlo study

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