Simulations Show New Phenomenon with Nanopore DNA Sequencing
XSEDE nanopore simulations could help improve medical diagnostics
By: Jorge Salazar
Molecular dynamics simulation of DNA capture and translocation through a graphene nanopore. Supercomputer simulations helped reveal a new phenomenon of water compression at the nanoscale. (Aleksei Aksimentiev)
Any truck operator knows that hydraulics do the heavy lifting. Water does the work because it's nearly incompressible at normal scales. But things behave strangely in nanotechnology, the control of materials at the scale of atoms and molecules.
Scientists discovered a surprising amount of water compression at the nanoscale by using XSEDE supercomputing resources. The findings could help advance medical diagnostics through creation of nanoscale systems that detect, identify, and sort biomolecules.
The unexpected effect comes from the action of an electric field on water in very narrow pores and in very thin materials. That's according to research by Aleksei Aksimentiev and James Wilson of the Department of Physics at the University of Illinois at Urbana–Champaign. They published their results in Physical Review Letters, June 2018.
Animation illustrating a 10 ns MD trajectory of a dsDNA molecule translocating through a nanopore in a graphene membrane under a 100 mV bias. Harmonic restraints were applied to the DNA molecule to maintain its coaxial arrangement with the nanopore. Graphene atoms are shown as gray spheres. Some graphene atoms are not shown to depict the location of the pore more clearly. (Aleksei Aksimentiev)
Size is everything when it came to the computational challenges of simulating the nanopores. "The problem is that we have to take into account the motion of every atom in our system," Aksimentiev said. "The systems typically are comprised of 100,000 atoms. That was critically important for the discovery of the phenomenon that we have done."
Supercomputer time was awarded through XSEDE. These allocations allowed the researchers use of the Stampede1 and Stampede2 systems at the Texas Advanced Computing Center; and Blue Waters at the National Center for Supercomputing Applications.
Aksimentiev credited XSEDE with a lion's share of the nanoscale study.
Animation illustrating a 20 ns MD trajectory of a dsDNA molecule failing to translocate through a graphene membrane under a 1 V bias. Harmonic restraints were applied to the DNA molecule to maintain its coaxial arrangement with the nanopore. Graphene atoms are shown as gray spheres. Some graphene atoms are not shown to depict the location of the pore more clearly. (Aleksei Aksimentiev)
"I would say that without XSEDE we would not be where we are in our project. Without XSEDE, I don't see how we would be able to accomplish the work that we do. It's not just this project. It's not just this system, but there are so many different systems that our group and other groups are investigating. What I like about XSEDE is that it gives access to diverse systems. The XSEDE portal itself is another benefit, because in one portal I can see everything that happens on all the machines. That makes it very easy to manage allocations and jobs," Aksimentiev said.
"Specifically to Stampede2," Aksimentiev continued, "we were able to run many simulations in parallel. It's not only that our individual simulation uses many cores of Stampede2. At the same time, we also had to run multi copy simulations, where many simulations run at the same time. That allowed us to measure the forces with the precision that allowed us to conclude about the nature of the physical phenomenon. It's been amazing how fast and how accurate the Stampede2 machine works."
James Wilson, a postdoctoral researcher working with Aksimentiev, added that " by running the simulations on Stampede2, I was able to finish twenty simulations in a couple of days, cutting down my time to solution immensely." He explained that just one NAMD molecular dynamics simulation would take about two weeks on local workstations.
Aleksei Aksimentiev and James Wilson, Department of Physics, University of Illinois at Urbana–Champaign
"The most important thing," Aksimentiev said, "is that highly accurate, precise simulations on big computers is a discovery tool. This work truly attributes to it, because we set out to do something else. We discovered a new phenomenon in nanopores. And we explain it through simulations. There's so many discoveries to be made with computers. That's why supercomputer research is worth funding."
The next step in this work, furthered Aksimentiev, is to see if the effect also occurs in biological channels and not just with the graphene membrane. They're also exploring the degree of sorting and separation possible for proteins, the cellular machinery of life. "Already in this paper we show that for one protein, we were able to differentiate variants. We'd like to apply it to more complex systems and also find conditions where the effect manifests at lower fields, which would expand its application to detection of biomarkers," Aksimentiev said.
The study, "Water-Compression Gating of Nanopore Transport," (doi: 10.1103/PhysRevLett.120.268101) was published June of 2018 in Physical Review Letters. The authors are Aleksei Aksimentiev and James Wilson of the University of Illinois at Urbana–Champaign. This work was supported by grants from the National Institutes of Health (Grants No. R01-GM114204 and No. R01 HG007406), and through a cooperative research agreement with the Oxford Nanopore Technologies. The authors gladly acknowledge supercomputer time provided through XSEDE Allocation Grant No. MCA05S028 and the Blue Waters petascale supercomputer system (UIUC).