Pictures of DNA often look very tidy – the strands of the double helix neatly wind around each other, making it seem like studying genetics should be relatively straightforward. In truth, these strands aren’t often so perfectly picturesque. They are constantly twisting, bending, and even being repaired by minuscule proteins. These are movements on the nanoscale, and capturing them for study is extremely challenging. Not only do they wriggle about, but the camera’s fidelity must be high enough to focus on the tiniest details.

Researchers from the University of Illinois Urbana-Champaign (U. of I.) have been working on resolving a grand challenge for molecular biology, and more specifically, genetic research: how to take a high-resolution image of DNA to facilitate study. Using a number of compute resources allocated through ACCESS, including the National Center for Supercomputing Application’s (NCSA) Delta, Pittsburgh Supercomputing Center’s (PSC) Bridges-2, San Diego Supercomputer Center’s (SDSC) Expanse, Purdue’s Rosen Center for Advanced Computing’s (RCAC) Anvil, and Texas Advanced Supercomputing Center’s (TACC) Stampede 3, Aleksei Aksimentiev, a professor of physics at U. of I, and Dr. Kush Coshic, formerly a graduate research assistant in the Center for Biophysics and Quantitative Biology and the Beckman Institute for Advanced Science and Technology at U. of I., and currently a postdoctoral fellow at the Max Planck Institute of Biophysics, recently made significant contributions to solving this challenge. They did it by focusing on two specific problems: creating a “camera” that could capture the molecular movement of DNA, and by creating an environment in which they could predictably direct the movement of the DNA strands.

“The fundamental problem we try to address is the gap between our ability to engineer DNA structures and our ability to predict and control their motion on 2D surfaces, a challenge which requires a deeper, molecular-level understanding to lay the groundwork for future biosensors and structural biology tools,” said Aksimentiev.

The team relied on massive, microsecond-long Molecular Dynamics (MD) simulations to computationally model the atomic interactions and validate their experimental setup, a task that demanded the immense parallel compute power that ACCESS-allocated resources can provide.

“While our work is fundamental, focusing on understanding the rules to build new tools, it lays essential groundwork for the precise control and guiding of biomolecules for next-generation medical diagnostics,” said Aksimentiev. “The GETvNA method serves as a powerful and low-cost platform for studying how single DNA molecules interact with proteins, a fundamental process in both health and disease. Its accessibility unlocks a wide range of applications, from enabling deeper biological research to offering a practical way to quantify the specific molecular interactions that are crucial for designing and testing new drugs.”

This research would have been impossible without the resources available through ACCESS resource providers. For research of this resource-intensive nature, Aksimentiev’s team had to utilize numerous resources; to get them, his team turned to the U.S. National Science Foundation ACCESS program. Through ACCESS, Aksimentiev was able to qualify for a “Maximize” allocation, granting him access to hundreds of thousands of compute hours on resources nationwide.

“NCSA resources, including Delta, were instrumental in enabling our microsecond-long simulations, currently the state-of-the-art, by reducing computation time from several months on personal machines to just a few days using high-performance computing,” said Aksimentiev.

For many years, the ACCESS, and its predecessor (XSEDE), program has been enabling our lab to perform computational discovery at the interface of biology and nanotechnology. Being able to use these state-of-the-art resources is pivotal to ensuring global leadership of U.S. science and the emergence of breakthrough technological innovations.

–Aleksei Aksimentiev, University of Illinois

The team has published results of their work in two papers: “Diffusion of DNA on Atomically Flat 2D Material Surfaces” in ACS Nano, and “Single-molecule dynamic structural biology with vertically arranged DNA on a fluorescence microscope” in Nature Methods. However, a researcher’s work is never truly over. Aksimentiev and his team will continue to expand upon their results.

“We would like to better understand from a molecular standpoint the milliseconds-to-seconds dynamics of the vertical standing DNA on the graphene surface,” said Aksimentiev. “Atomistic simulations cannot be used to probe such timescales, and instead, we will use our microsecond-long atomistic trajectories to calibrate coarser resolution models such as our in-house mrDNA method that we previously used to unravel the physical process of viral genome packaging inside the virus’s protein capsid.”

You can read a detailed breakdown of this research in the original story: Capturing and Controlling the Movement of Genes

Resource Provider Institution(s): National Center for Supercomputing Application (NCSA), Pittsburgh Supercomputing Center (PSC), San Diego Supercomputer Center (SDSC) Expanse, Purdue Rosen Center for Advanced Computing (RCAC), Texas Advanced Supercomputing Center (TACC)
Resources Used: Delta, Bridges-2, Expanse, Anvil, Stampede 3
Affiliations: University of Illinois Urbana-Champaign
Funding Agency: NSF 
Grant or Allocation Number(s): MCA05S028

The science story featured here was enabled by the U.S. National Science Foundation’s ACCESS program, which is supported by National Science Foundation grants #2138259, #2138286, #2138307, #2137603, and #2138296.