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Comparative analysis of nucleotide translocation through protein nanopores using steered molecular dynamics and an adaptive biasing force.

Martin, HS; Jha, S; Coveney, PV; (2014) Comparative analysis of nucleotide translocation through protein nanopores using steered molecular dynamics and an adaptive biasing force. J Comput Chem , 35 (9) pp. 692-702. 10.1002/jcc.23525. Green open access

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Abstract

The translocation of nucleotide molecules across biological and synthetic nanopores has attracted attention as a next generation technique for sequencing DNA. Computer simulations have the ability to provide atomistic-level insight into important states and processes, delivering a means to develop a fundamental understanding of the translocation event, for example, by extracting the free energy of the process. Even with current supercomputing facilities, the simulation of many-atom systems in fine detail is limited to shorter timescales than the real events they attempt to recreate. This imposes the need for enhanced simulation techniques that expand the scope of investigation in a given timeframe. There are numerous free energy calculation and translocation methodologies available, and it is by no means clear which method is best applied to a particular problem. This article explores the use of two popular free energy calculation methodologies in a nucleotide-nanopore translocation system, using the α-hemolysin nanopore. The first uses constant velocity-steered molecular dynamics (cv-SMD) in conjunction with Jarzynski's equality. The second applies an adaptive biasing force (ABF), which has not previously been applied to the nucleotide-nanpore system. The purpose of this study is to provide a comprehensive comparison of these methodologies, allowing for a detailed comparative assessment of the scientific merits, the computational cost, and the statistical quality of the data obtained from each technique. We find that the ABF method produces results that are closer to experimental measurements than those from cv-SMD, whereas the net errors are smaller for the same computational cost. © 2014 Wiley Periodicals, Inc.

Type: Article
Title: Comparative analysis of nucleotide translocation through protein nanopores using steered molecular dynamics and an adaptive biasing force.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jcc.23525
Publisher version: http://dx.doi.org/10.1002/jcc.23525
Additional information: © 2014 The Authors Journal of Computational Chemistry Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: DNA, adaptive biasing force, molecular dynamics, nanopore, protein
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/1426713
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