J. Comer and A. Aksimentiev.
Predicting the DNA sequence dependence of nanopore ion current
using atomic-resolution Brownian dynamics.
Journal of Physical Chemistry C, 116:3376-3393, 2012.
COME2012-AA
It has become possible to distinguish DNA molecules of different nucleotide sequences
by measuring ion current passing through a narrow pore containing DNA. To assist
experimentalists in interpreting the results of such measurements and to improve the DNA
sequence detection method, we have developed a computational approach that has both
the atomic-scale accuracy and the computational efficiency required to predict DNA
sequence-specific differences in the nanopore ion current. In our Brownian dynamics
method, the interaction between the ions and DNA is described by three-dimensional
potential of mean force maps determined to a 0.03 nm resolution from all-atom molecular
dynamics simulations. While this atomic-resolution Brownian dynamics method produces
results with orders of magnitude less computational effort than all-atom molecular
dynamics requires, we show here that the ion distributions and ion currents predicted by
the two methods agree. Finally, using our Brownian dynamics method, we find that a small
change in the sequence of DNA within a pore can cause a large change in the ion current,
and validate this result with all-atom molecular dynamics.
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