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.
Spotlight: DNA Nanosensors Designed Computationally (Feb 2016)
DNA sequencing is achieved by following a strand of DNA at a speed that permits recognition of the DNA bases in their actual order, thousands of bases or more for each pass. Nanotechnology can assist in the task, in principle, by furnishing sensors that can resolve single DNA bases and nano-mechanical actuators that pull the DNA in a controlled fashion passing through the sensor. Instead of building and testing actual sensors and actuators it is cheaper and faster to simulate them. Nanoengineers have indeed succeeded with such simulations over the last decade focussing on silicon technology (see October
2004 highlight: Transistor Meets DNA). Now the engineers have moved with their simulations to graphene technology that promises much better resolving power as sensors are thinner and as signals can be detected electronically in graphene (December
2013 and November
2014 highlights). The main unsolved problem is the mechanical actuator: how can one control movement of DNA through a graphene sensor such that measured signals become less noisy and bases can be recognized? A recent study, based on molecular dynamics simulations with NAMD and quantum electronics calculations of graphene, suggests use of an actuator that simultaneously stretches the DNA and pulls it through the sensor. This manipulation leads to a stepwise translocation of DNA through the graphene nanosensor, slowing down DNA translocation and stabilizing DNA bases inside the sensor. Read more 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.