title: Water Mediates Recognition of DNA Sequence via Ionic Current Blockade in a Biological Nanopore.
abstract: Electric field-driven translocation of DNA strands through biological nanopores has been shown to produce blockades of the nanopore ionic current that depend on the nucleotide composition of the strands. Coupling a biological nanopore MspA to a DNA processing enzyme has made DNA sequencing via measurement of ionic current blockades possible. Nevertheless, the physical mechanism enabling the DNA sequence readout has remained undetermined. Here, we report the results of all-atom molecular dynamics simulations that elucidated the physical mechanism of ionic current blockades in the biological nanopore MspA. We find that the amount of water displaced from the nanopore by the DNA strand determines the nanopore ionic current, whereas the steric and base-stacking properties of the DNA nucleotides determine the amount of water displaced. Unexpectedly, we find the effective force on DNA in MspA to undergo large fluctuations, which may produce insertion errors in the DNA sequence readout.
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign , 1110 West Green Street, Urbana, Illinois 61801, United States.
authors.forename: Swati
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign , 1110 West Green Street, Urbana, Illinois 61801, United States.|Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign , 1110 West Green Street, Urbana, Illinois 61801, United States.
authors.forename: Jejoong
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign , 1110 West Green Street, Urbana, Illinois 61801, United States.|Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign , 1110 West Green Street, Urbana, Illinois 61801, United States.|Beckman Institute for Advanced Science and Technology , 405 North Mathews M/C 251, Urbana, Illinois 61801, United States.
authors.forename: Aleksei
authors.initials: A
authors.lastname: Aksimentiev
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000032:analysis*; D004560:Electricity; D017136:Ion Transport; D056004:Molecular Dynamics Simulation; D058608:Nanopores; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry; D017422:Sequence Analysis, DNA / Q000379:methods*; D014867:Water / Q000737:chemistry*
chemical_list: D009711:Nucleotides; D014867:Water; D004247:DNA
keywords: blockade current; molecular dynamics; nanopore sequencing; nucleic acids; solvation