The University of Southampton
University of Southampton Institutional Repository

Translocation of flexible and tensioned ssDNA through in silico designed hydrophobic nanopores with two constrictions

Translocation of flexible and tensioned ssDNA through in silico designed hydrophobic nanopores with two constrictions
Translocation of flexible and tensioned ssDNA through in silico designed hydrophobic nanopores with two constrictions
Protein-inspired nanopores with hydrophobic constriction regions have previously been shown to offer some promise for DNA sequencing. Here we explore a series of pores with two hydrophobic constrictions. The impact of nanopore radius, the nature of residues that define the constriction region and the flexibility of the ssDNA is explored. Our results show that aromatic residues slow down DNA translocation, and in the case of short DNA strands, they cause deviations from a linear DNA conformation. When DNA is under tension, translocation is once again slower when aromatic residues are present in the constriction. However, the lack of flexibility in the DNA backbone provides a narrower window of opportunity for the DNA bases to be retained inside the pore via interaction with the aromatic residues, compared to more flexible strands. Consequently, there is more variability in translocation rates for strands under tension. DNA entry into the pores is correlated to pore width, but no such correlation between width and translocation rate is observed.
2040-3364
1673-1679
Rattu, Punam
70569439-229e-4c6e-b313-f908d259777d
Belzunces, Bastien
c3e44761-ce37-4f13-b551-78f970d7e588
Haynes, Taylor
1180690e-8075-457a-8bb2-d4561a59521a
Skylaris, Chris-Kriton
8f593d13-3ace-4558-ba08-04e48211af61
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Rattu, Punam
70569439-229e-4c6e-b313-f908d259777d
Belzunces, Bastien
c3e44761-ce37-4f13-b551-78f970d7e588
Haynes, Taylor
1180690e-8075-457a-8bb2-d4561a59521a
Skylaris, Chris-Kriton
8f593d13-3ace-4558-ba08-04e48211af61
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394

Rattu, Punam, Belzunces, Bastien, Haynes, Taylor, Skylaris, Chris-Kriton and Khalid, Syma (2021) Translocation of flexible and tensioned ssDNA through in silico designed hydrophobic nanopores with two constrictions. Nanoscale, 13 (3), 1673-1679. (doi:10.1039/D0NR04890A).

Record type: Article

Abstract

Protein-inspired nanopores with hydrophobic constriction regions have previously been shown to offer some promise for DNA sequencing. Here we explore a series of pores with two hydrophobic constrictions. The impact of nanopore radius, the nature of residues that define the constriction region and the flexibility of the ssDNA is explored. Our results show that aromatic residues slow down DNA translocation, and in the case of short DNA strands, they cause deviations from a linear DNA conformation. When DNA is under tension, translocation is once again slower when aromatic residues are present in the constriction. However, the lack of flexibility in the DNA backbone provides a narrower window of opportunity for the DNA bases to be retained inside the pore via interaction with the aromatic residues, compared to more flexible strands. Consequently, there is more variability in translocation rates for strands under tension. DNA entry into the pores is correlated to pore width, but no such correlation between width and translocation rate is observed.

Text
nanopores_revision_NH - Accepted Manuscript
Download (2MB)
Text
Supp_info_revised_2020_11_16
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 20 December 2020
e-pub ahead of print date: 6 January 2021
Published date: 21 January 2021
Additional Information: Funding Information: PR and TH are funded by Oxford Nanopore Technologies. SK is funded by EPSRC. BB is Funded by the Leverhulme Trust. Funding Information: The authors thank Mark Sansom and Shanlin Rao for helpful discussions. BB is supported by the Leverhulme Trust and PR is supported by Oxford Nanopore Technologies Ltd. The authors acknowledge the use of the IRIDIS High Performance Computing Facility, and associated support services at the University of Southampton and the use of the UK national supercomputer, ARCHER granted via the UK High-End Computing Consortium for Biomolecular Simulation, HECBioSim (http://hecbiosim.ac.uk), supported by EPSRC (grant no. EP/R029407/1), in the completion of this work. The Michael supercomputer was used for the DFT calculations for which the authors thak the MMM Hub. Publisher Copyright: © 2021 The Royal Society of Chemistry.

Identifiers

Local EPrints ID: 445984
URI: http://eprints.soton.ac.uk/id/eprint/445984
ISSN: 2040-3364
PURE UUID: 0d225a9d-172b-4b43-919b-af3adffb1953
ORCID for Chris-Kriton Skylaris: ORCID iD orcid.org/0000-0003-0258-3433
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

Catalogue record

Date deposited: 18 Jan 2021 17:31
Last modified: 06 Jun 2024 04:21

Export record

Altmetrics

Contributors

Author: Punam Rattu
Author: Bastien Belzunces
Author: Taylor Haynes
Author: Syma Khalid ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×