COVID-19 may have dominated headlines and occupied much of the world’s scientific computing capacity over the last year, but many researchers continued their work to keep other deadly viruses at bay. One of those, Ebola, continues to cause deaths throughout Africa, despite a vaccine developed less than two years ago. Over that time, researchers at the University of Delaware have been using supercomputing power allocated by the Extreme Science and Engineering Discovery Environment (XSEDE) to help identify improved drug targets on the Ebola virus.
The study, led by Juan Perilla, an assistant professor of chemistry and biochemistry at the University of Delaware, zeroed in on the Ebola virus’ nucleocapsid, a shell of proteins that encases and protects the virus’ RNA. If the nucleocapsid could be breached, the RNA could be compromised and the virus could be prevented from replicating. Perilla and his colleagues wanted to know what made that nucleocapsid tick.
To examine the nucleocapsid, the researchers needed high-power supercomputers for intensive simulations. Those resources were provided by XSEDE: specifically, time on the Bridges system at the Pittsburgh Supercomputing Center and on the Stampede2 system at the Texas Advanced Computing Center (TACC).
Using those systems, the team ran a molecular dynamics simulation of the Ebola nucleocapsid encompassing its 4.8 million atoms, resting in sodium chloride ions that mimicked the cellular environs in which the nucleocapsids are found. Two variants of this simulation were used: one with the RNA inside, one without.
“What we’ve found is that the Ebola virus has evolved to regulate the stability of the nucleocapsid by forming electrostatic interactions with its RNA, its genetic material,” Perilla said in an interview with TACC’s Jorge Salazar. “There is an interplay between the RNA and the nucleocapsid that keeps it together.” The researchers discovered this because in the simulation without the RNA inside the nucleocapsid, the nucleocapsid began to lose its structural integrity over time.
Based on the results, the researchers are continuing to explore ways to attack the Ebola virus. Perilla suggested, for instance, that it might be easier to overstabilize the virus to halt its replication, than it would be to destabilize it. The researchers noted that this approach might also prove fruitful with other viruses, such as coronaviruses or hepatitis B.
To test these ideas, and others, the researchers are now scaling their research up on the Frontera supercomputer, also hosted by TACC.
“Frontera is part of the TACC infrastructure,” Perilla said. “We knew what developmental tools were going to be there, and also the queueing system and other intricacies of these machines. That helped a lot. In terms of architecture, we’re familiar with Stampede2, although this is a different machine. Our experience with Stampede2 allowed us to move quickly to start using Frontera.”
To read more about this research, visit TACC’s Jorge Salazar’s article here.