Nanopore Detector based analysis of single-molecule conformational kinetics and binding interactions.
BACKGROUND
A Nanopore Detector provides a means to transduce single molecule events into observable channel current changes. Nanopore-based detection can report directly, or indirectly, on single molecule kinetics. The nanopore-based detector can directly measure molecular characteristics in terms of the blockade properties of individual molecules--this is possible due to the kinetic information that is embedded in the blockade measurements, where the adsorption-desorption history of the molecule to the surrounding channel, and the configurational changes in the molecule itself, imprint on the ionic flow through the channel. This rich source of information offers prospects for DNA sequencing and single nucleotide polymorphism (SNP) analysis. A nanopore-based detector can also measure molecular characteristics indirectly, by using a reporter molecule that binds to certain molecules, with subsequent distinctive blockade by the bound-molecule complex.


RESULTS
It is hypothesized that reaction histories of individual molecules can be observed on model DNA/DNA, DNA/Protein, and Protein/Protein systems. Preliminary results are all consistent with this hypothesis. Nanopore detection capabilities are also described for highly discriminatory biosensing, binding strength characterization, and rapid immunological screening.


CONCLUSIONS
In essence, the heart of chemistry is now accessible to a new, single-molecule, observation method that can track both external molecular binding states, and internal conformation states.
Winters-Hilt
Stephen
S
Department of Computer Science, University of New Orleans, New Orleans, LA 70148, USA. winters@cs.uno.edu
D001483:Base Sequence; D019295:Computational Biology; D004247:DNA / Q000032:analysis* / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D049329:Nanostructures / Q000032:analysis* / Q000737:chemistry / Q000648:ultrastructure; D009690:Nucleic Acid Conformation; D016062:Porosity; D011506:Proteins / Q000032:analysis* / Q000737:chemistry
D011506:Proteins; D004247:DNA