title: The effects of diffusion on an exonuclease/nanopore-based DNA sequencing engine.
abstract: Over 15 years ago, the ability to electrically detect and characterize individual polynucleotides as they are driven through a single protein ion channel was suggested as a potential method for rapidly sequencing DNA, base-by-base, in a ticker tape-like fashion. More recently, a variation of this method was proposed in which a nanopore would instead detect single nucleotides cleaved sequentially by an exonuclease enzyme in close proximity to one pore entrance. We analyze the exonuclease/nanopore-based DNA sequencing engine using analytical theory and computer simulations that describe nucleotide transport. The available data and analytical results suggest that the proposed method will be limited to reading <80 bases, imposed, in part, by the short lifetime each nucleotide spends in the vicinity of the detection element within the pore and the ability to accurately discriminate between the four mononucleotides.
authors.affiliation: Department of Physics, Virginia Commonwealth University, Richmond, Virginia 23284, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Reiner
authors.forename: Arvind
authors.initials: A
authors.lastname: Balijepalli
authors.forename: Joseph W F
authors.initials: JW
authors.lastname: Robertson
authors.forename: Bryon S
authors.initials: BS
authors.lastname: Drown
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Burden
authors.forename: John J
authors.initials: JJ
authors.lastname: Kasianowicz
mesh_terms: D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D003854:Deoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D004058:Diffusion; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D058608:Nanopores; D009690:Nucleic Acid Conformation; D011336:Probability; D011487:Protein Conformation; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D003854:Deoxyribonucleotides; D004247:DNA; D005090:Exodeoxyribonucleases