Apr 1, 2014
Using solid-state nanopores to examine proteins
While much of the focus in developing solid-state nanopores has been on applications in DNA sequencing, they can also be used to examine the state of proteins on a molecule-by-molecule basis. By examining small changes in the characteristics of proteins as they pass through nanopores it is hoped to be able to measure the interactions between the protein and small drug molecules. Reporting in Nanotechnology, recent work by IBM researchers in Melbourne sheds light on this.
The team used high-performance supercomputers to predict the change in conductance of silicon nitride nanopores during the brief moments that proteins occupy the pore during translocation. For a pore that had an hourglass profile, they found that the conductance was sensitive to the position of the protein, with a smaller drop in conductance if the protein was placed at the pore entrance instead of its centre. For high concentrations of proteins, situations might arise where more than one protein occupies the nanopore at a time. This was also considered in the calculations with the result that the change in conductance does not quite scale linearly with the number of proteins within the pore, instead it is a complex function of their position.
Time-dependent properties of the translocation process were also considered by performing steered molecular dynamics simulations to guide proteins through the pore at a rate accessible to computational methods. From this the variation in the drag coefficient of the protein due to the confined geometry of the pore could be monitored.
Taken together, the results from the position-dependent and the steered simulations help give molecular-level insight into the two key quantities that experimental researchers commonly use to characterize the translocation process: the magnitude of the current drop and its duration.
More information can be found in the journal Nanotechnology 25 155502.
About the author
Matthew Downton is a research staff member at the IBM Research Collaboratory for Life Sciences Melbourne. His co-authors are Sridhar Kumar Kannam, Sung Cheol Kim, Priscilla Rogers, Natalie Gunn, John Wagner and Stefan Harrer. They are part of a team of IBM Researchers in Melbourne working on developing uses of nanotechnology to tackle problems in biotechnology.