As supercomputers around the world spin up to combat the coronavirus, the Texas Advanced Computing Center (TACC) is announcing results that may help to illuminate COVID-19, as well as other virus and DNA replication tasks. TACC’s Jorge Salazar highlighted the research, which was conducted by a group of researchers from Boston University, the University of California San Diego and the University of Wisconsin-Madison.

The research comprised two studies, with the first focusing on cell membranes. When viruses like COVID-19 invade, they force host cells to bend and set free the copies of the virus created within the cell (a process known as “budding”). The researchers examined these cell membranes, zeroing in on a specific protein that is suspected to be largely responsible for the budding process. With experimental techniques too low-resolution to study the necessary interactions, the researchers turned to supercomputer-powered simulation.

Using atomistic molecular dynamics simulations, the researchers carefully examined the filaments of the target protein. The goal: to establish whether the atomistic forces within the protein were responsible for the bending, and thus, the budding. These simulations, which included up to two million atoms, were allotted supercomputing time through the NSF’s Extreme Science and Engineering Discovery Environment (XSEDE) program. They ran on TACC’s Stampede2 system, a Dell EMC system equipped with Intel Xeon Phi CPUs that delivers 10.7 Linpack petaflops and ranked 18th on the latest Top500 list of the world’s fastest supercomputers.

“Supercomputers with massive parallelization are very much required to push the boundary of biomolecular simulations,” Qiang Cui, a professor of chemistry, physics and biomedical engineering at Boston University who worked on both studies, told Salazar. “Stampede2 has been crucial for us to set up these relatively large-scale membrane simulations.”

The results of the simulations lent new insight into how the bending occurs, including a “clear intrinsic twist” in the protein.

“Membrane remodeling is an important process that underlies many crucial cellular functions and events, such as synaptic transmission and virus infection,” Cui said. “Understanding the mechanism of membrane remodeling will help propose new strategies for battling human diseases due to impaired membrane fusion activities – or preventing viral infection – a timely topic these days given the quick spread of the new coronavirus.”

The second study also used supercomputer simulations – this time, to examine the chemical processes that govern how nucleotide bases are added to strands of DNA. 

“Our role was to do these molecular dynamics simulations and test different models for how the atoms are moving around during the reaction and test different interactions that are helping that along,” explained Daniel Roston, an assistant project scientist at the University of California San Diego. To run these simulations, they used 500,000 CPU hours on the Comet system at the San Diego Supercomputer Center (SDSC). Comet’s 1,944 Intel Haswell nodes and 72 Nvidia GPU nodes deliver 2.76 peak petaflops.

“One of the great things about XSEDE is that we can take advantage of a ton of computational power,” Roston said. “DNA replication is what life is about. We’re getting at the heart of how that happens, the really fundamental process to life as we know it on Earth. This is so important, we should really understand how it works at a deep level.”

About the research

The first study was written by Taraknath Mandal, Wilson Lough, Saverio E. Spagnolie, Anjon Audhya and Qiang Cui. It was published as “Molecular Simulation of Mechanical Properties and Membrane Activities of the ESCRT-III Complexes” in the February 2020 issue of Biophysical Journal and can be found here.

The second study was written by Daniel Roston, Darren Demapan and Qiang Cui. It was published as “Extensive free-energy simulations identify water as the base in nucleotide addition by DNA polymerase” in the December 2019 issue of PNAS and can be accessed here. 

To read Jorge Salazar’s original article covering this research, click here.

Header image: Virus budding. Image courtesy of Mandal et al.