Nanoscale holes in solid-state membranes, so-called nanopores, furnish nanosensors for probing biological molecules such as DNA and protein. Under electric fields, charged molecules like DNA are pushed through these pores and the flow of ions surrounding the translocating DNA can be recorded to recognize individual DNA bases, and in turn, the sequence of DNA. Traditional nanopore sensors often use solid-state membranes, which are too thick to recognize single bases on a DNA strand. This limitation can be overcome by using two-dimensional materials such as graphene or MoS$_2$. Only a single base pair of DNA fits into the thin two-dimensional material nanopores at any time, such that these nanopores can potentially provide single-base resolution for DNA sensing. In addition, graphene and MoS$_2$ are both lectrically conductive, thereby allowing the use of electric current in the layer to detect and characterize the DNA in the pore. Instead of actually building and testing the device experimentally, molecular dynamics simulations can assist and enable a bottom-up design of two-dimensional material nanopore devices by unveiling the atomic-level processes occurring during nanopore sensing.
Threading DNA through a nanometer-size pore, so called
nanopores, drilled into an ultrathin graphene membrane is a promising
approach to build nanobiosensors for sequencing the human genome. Graphene
nanopores can detect translocating DNA by recording concomitant flow of
charged ions through the pore (see December
2011 highlight). As reported in the December
2013 highlight, graphene, which is an electrical conductor, offers a new
way of sensing DNA molecules by monitoring sheet currents along the graphene
membrane. DNA is a highly extensible molecule and upon mechanical manipulation can
change its structure from a canonical helical conformation to a linear
zipper-like conformation. A new study, which
combines classical molecular dynamics simulations using NAMD with quantum mechanical
simulations, suggests that sheet currents, in graphene membranes, can be used
to detect conformation and sequence of
a DNA molecule passing through the nanopore. This new research will guide the
development of graphene-based nanosensors for DNA detection.
More information can be found on our graphene nanopore website.
Computer modeling in biotechnology, a partner in development.
Aleksei Aksimentiev, Robert Brunner, Jordi Cohen, Jeffrey Comer, Eduardo Cruz-Chu, David Hardy, Aruna Rajan, Amy Shih, Grigori Sigalov, Ying Yin, and Klaus Schulten. In Protocols in Nanostructure Design, Methods in Molecular Biology, pp. 181-234. Humana Press, 2008.
Beyond the gene chip.
J. B. Heng, A. Aksimentiev, C. Ho, V. Dimitrov, T. Sorsch, J. Miner, W. Mansfield, K. Schulten, and G. Timp. Bell Labs Technical Journal, 10:5-22, 2005.
Sizing DNA using a nanometer-diameter pore.
J. B. Heng, C. Ho, T. Kim, R. Timp, A. Aksimentiev, Y. V. Grinkova, S. Sligar, K. Schulten, and G. Timp. Biophysical Journal, 87:2905-2911, 2004.
