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Conformational fluctuations of a DNA electrophoretically translocating through a nanopore under the action of a motor protein

  • Harshwardhan H. Katkar
  • Murugappan MuthukumarEmail author
Regular Article
  • 78 Downloads
Part of the following topical collections:
  1. Polymers: From Adsorption to Translocation - Topical Issue in Memoriam Loïc Auvray (1956-2016)

Abstract.

Single-file single-molecule electrophoresis through a nanopore has emerged as one of the successful methods in DNA sequencing. In gaining sufficient accuracy in the readout of the sequence, it is essential to position every nucleotide of the sequence with great accuracy and precision at the interrogation point of the nanopore. A combination of a ratcheting enzyme and a threaded DNA across a protein pore under an electric field is experimentally shown to be a viable method for DNA sequencing within the single-molecule electrophoresis technique. Using coarse-grained models of the enzyme and the protein nanopore, and Langevin dynamics simulations, we have characterized the conformational fluctuations of the DNA inside the nanopore. We show that the conformational fluctuations of DNA are significant for slowly operating enzymes such as phi29 DNA polymerase. Our results imply that there is considerable uncertainty in precisely positioning a nucleotide at the interrogation point of the nanopore. The discrepancy between the results of coarse-grained simulations and the experimentally successful accurate sequencing suggests that additional features of the experiments, such as explicit treatment of electrolyte ions and hydrodynamics, must be incorporated in the simulations to accurately model experimental constructs.

Graphical abstract

Keywords

Polymers: From Adsorption to Translocation - Topical Issue in Memoriam Loïc Auvray (1956-2016) 

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Copyright information

© EDP Sciences, Società Italiana di Fisica / Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Harshwardhan H. Katkar
    • 1
    • 2
  • Murugappan Muthukumar
    • 2
    Email author
  1. 1.Department of ChemistryThe University of ChicagoChicagoUSA
  2. 2.Department of Polymer Science and EngineeringUniversity of MassachusettsAmherstUSA

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