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American Chemical Society, ACS Nano, 8(6), p. 6960-6968, 2012

DOI: 10.1021/nn3019943

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Molecular Dynamics Study of MspA Arginine-Mutants Predicts Slow DNA Translocations and Ion Current Blockades Indicative of DNA Sequence

This paper is available in a repository.
This paper is available in a repository.

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Abstract

The protein nanopore Mycobacteria smegmatis porin A (MspA), can be used to sense individual nucleotides within DNA, potentially enabling a technique known as nanopore sequencing. In this technique, single stranded DNA electrophoretically moves through the nanopore and results in an ionic current that is nucleotide-specific. However, with a high transport velocity of the DNA within the nanopore, the ionic current cannot be used to distinguish signals within noise. Through extensive (~100 μs in total) all-atom molecular dynamics simulations, we examine the effect of positively charged residues on DNA translocation rate and the ionic current blockades in MspA. Simulation of several arginine mutations show a ~10–30 fold reduction of DNA translocation speed without eliminating the nucleotide induced current blockages. Comparison of our results with similar engineering efforts on a different nanopore (alpha-hemolysin) reveals a non-trivial effect of nanopore geometry on the ionic current blockades in mutant nanopores.