While HIV virus mortality rates have dropped, it remains a threat. As such, a multi-institutional team of researchers is using supercomputer simulation to discover the secrets of the HIV-1 virus, how it invades a cell and then replicates itself. The team’s discovery, published in Nature, suggests that a naturally occurring small molecule named inositol hexakisphosphate (IP6) plays a role in the lifecycle of the HIV-1 virus by forming a protective bubble capsule for copies of its genes. The goal of the research is to learn how the HIV virus grows in order to develop therapies or drugs to stop the HIV-1 virus.
Juan R. Perilla, Ph.D., assistant professor at the Department of Chemistry and Biochemistry, University of Delaware (UD), and his team continue to study the HIV-1 virus.
“Our primary focus is on what happens after the virus is in a healthy cell and hijacks the cellular machinery. We study large protein complexes, involving thousands of proteins,” Perilla says. “The problem requires that we establish new theoretical and computational tools for the successful elucidation of protein dynamics as well as the emergent properties which arise from the interactions between hundreds of millions of atoms. Our work is not possible without using supercomputers for simulation and analysis. Certainly, the time we save is in the tens of years’ time scale.”
The HIV-1 virus has a life cycle with different stages. HIV’s life cycle primarily occurs at the interior of a human cell. After the virus goes into the cytoplasm, the virus is capable of hijacking essential cell machinery.
Figure 1 shows the helical assembly of the HIV virus. The virus encases its genome in a protein shell, referred to as a capsid. The capsid follows geometrical arrangements that resemble polyhedrons and spirals. The spirals arrange themselves into tubular forms. The back portion of the image shows cryoEM images of the assembled tubes. The front displays a computational reconstruction of such tubes at atomic resolution, atom by atom.
Many experimental techniques are just a snapshot of a single cell that cannot show the interaction that occurs at the cellular level. In 2013, a Nobel prize was awarded for computational modeling research that was later termed the “computational microscope.”
“The computational microscope enables us to combine multimodal experimental data in a single platform. Using supercomputers, we are able to look at much larger complexes and time-scales than those available to single node computers,” Perilla says.
Perilla and his research team used a large number of supercomputers, including the National Science Foundation Blue Waters, Pittsburgh Supercomputing Center Bridges and Stampede2 supercomputer located at the Texas Advanced Computing Center (TACC), University of Texas at Austin. These supercomputers provide massive computational power over the typical research cluster computer. For example, the TACC Stampede2 supercomputer is one of the most powerful and significant current supercomputers in the U.S. for open science research. Stampede2 is an 18-petaflop system containing 4,200 Intel Xeon Phi nodes, and it uses Intel Xeon Scalable processors and Intel Omni-Path Architecture.
Investigators used specialized software in the HIV-1 replications research to take advantage of the multicore and parallel processing capabilities of today’s supercomputers. The team used NAMD2 (version two of the Nanoscale Molecular Dynamics software), which is noted for its parallel computational efficiency and is often used to simulate large systems with millions of atoms.
“We used NAMD2 heavily, as it is finely tuned for all the national supercomputers and has been under active development for nearly two decades. We also develop analysis tools that we incorporate into visual molecular dynamics to make them accessible for other researchers,” Perilla notes. “In addition, we develop techniques to incorporate experimental data into our simulations. Our team also uses the Intel Math Kernel Libraries (MKL) and Intel compilers in most of our analysis and simulations.”
Perilla and team plan to use even more powerful supercomputers, such as the Frontera system to be deployed at TACC, which will be the fastest supercomputer at any U.S. university.
The National Science Foundation (NSF) awarded TACC $60 million to deploy the new supercomputer Frontera (Spanish for “frontier”), which will begin operations this year. The primary computing system will be provided by Dell EMC and is powered by next-generation an Intel Xeon Scalable Cascade Lake advanced performance processor. Among the most powerful supercomputers in the world, the scale and power of the Frontera system will aid researchers in finding new discoveries and advancements in important work such as HIV research.
Scientists are trying to learn the mechanisms of the HIV-1 virus to learn how it enters a normal cell, grows and replicates itself. Research by Perilla’s team uses supercomputer modeling to study the building blocks of the HIV-1 virus and how it moves in time.
“Our research provides information that can be used in developing drug therapies to combat the spread of HIV-1 virus. Because our work requires analysis of interactions between hundreds up to millions of atoms, it is critical to have the most advanced supercomputers and software available. In the future, we need supercomputer hardware that has more dense nodes, a high number of cores and lower latency to allow us to see the real-time cellular functions of the HIV-1 virus,” Perilla says.
Linda Barney is the founder and owner of Barney and Associates, a technical/marketing writing, training and web design firm in Beaverton, OR.
This article was produced as part of Intel’s HPC editorial program, with the goal of highlighting cutting-edge science, research and innovation driven by the HPC community through advanced technology. The publisher of the content has final editing rights and determines what articles are published.
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