Jülich Researchers Utilize JUWELS Supercomputer to Find New Starting Point for HIV Therapies 

February 28, 2024

Feb. 28, 2024 — Molecular simulations on the JUWELS supercomputer show how the HIV-1 virus is able to evade the human immune system. The newly discovered mechanism could prove to be the Achilles’ heel of the virus and open new doors for HIV therapies.

Dr. Holger Gohlke is head of the “Structure-based Bioinformatics” team at Forschungszentrum Jülich’s IBG-4 subinstitute and the “Computational Pharmaceutical Chemistry and Molecular Bioinformatics” research group at Heinrich Heine University Düsseldorf. Photo credit: Forschungszentrum Jülich.

HIV infections and AIDS are among the most common and threatening infectious diseases worldwide. Highly effective therapies are now available. However, a complete cure or vaccination that protects against infection is not yet possible.

Researchers now believe that the virus has jumped from chimpanzees and gorillas to humans several times. Using molecular dynamics simulations on the JUWELS supercomputer at Forschungszentrum Jülich, Prof. Holger Gohlke from Forschungszentrum Jülich and Heinrich Heine University Düsseldorf and Prof. Carsten Münk from the University Hospital of Düsseldorf have now been able to understand in detail for the first time a step through which the virus has adapted to human cells.

Prof. Gohlke, what was the motivation for this study?

Prof. Holger Gohlke: HIV-1 viruses are the evolutionary result of rare successful transmissions of the simian immunodeficiency virus (SIV) to humans. Humans are immune to SIV. We therefore wondered how the pandemic group HIV-M is able to evade the human immune system. There are also other, nonpandemic strains (HIV-N, HIV-O and HIV-P groups), which are very rare and have only been found in a few people infected in West Africa.

Vertebrates use several cellular restriction factors to prevent the replication, i.e. multiplication, of HIV. However, it has so far remained unclear whether the low incidence of non-M HIVs is related to the activity of these antiviral factors, i.e. whether they limit the spread of the virus among humans. There is a particular focus here on TRIM5α, a protein that is found in the cells of most primates and is effective against various infections and retroviruses.

TRIM5α binds to the capsid, the shell that encloses the viral genome. The activity of this protein is partly dependent on cyclophilin A (CYPA), another protein which has catalytic properties, i.e. it is able to accelerate certain reactions. One of the main objectives of this work was to understand the mechanism.

What particular challenges were associated with the molecular dynamics simulations?

Gohlke: To start the simulations, a structural model of the HIV-1 M capsid first had to be produced with CYPA, which was then used to generate the other complexes for HIV-N, HIV-O, and HIV-P as well as other variants through “mutations in the computer”. To assess the influence of CYPA on TRIM5, biased MD simulations were performed to simulate the conversion catalyzed by CYPA in the capsid. In addition, the conversion in the capsid without CYPA was simulated for comparison.

A total of 16 systems were simulated, with 121 individual steps for each system. This resulted in a high number of independent simulations that had to be performed. The simulations also had to be extensive in order to obtain highly precise results. This was necessary to gain detailed insights into the subtle differences between the various HIV groups and the role of CYPA.

The JUWELS supercomputer at Forschungszentrum Jülich. Credit: Forschungszentrum Jülich/Sascha Kreklau.

What is the potential of the weak spot you have discovered in terms of the treatment of HIV?

Gohlke: The results of our simulations indicate that the speed of the reaction catalyzed by CYPA may play a crucial role in the protection of HIV-1 M and, therefore, in its pandemic property. Our data suggest that CYPA subtly alters the capsid – the shell that encloses the viral genome. These induced changes appear to have a severe impact on the viral infection. It is the binding of CYPA which likely ensures that the human HIV-1 M virus is protected from the antiviral protein TRIM5α. The study has therefore identified a new “weak spot” of HIV-1 and could lead to new HIV-1 drugs that suppress the binding of CYPA to the virus in the cell or modulate the activity of CYPA.

Original Publication:

Augustin P. Twizerimana, Daniel Becker, Shenglin Zhu, Tom Luedde, Holger Gohlke, and Carsten Münk
The cyclophilin A-binding loop of the capsid regulates the human TRIM5α sensitivity of nonpandemic HIV-1
Proceedings of the National Academy of Sciences (PNAS), 2023, DOI: 10.1073/pnas.2306374120


Source: Forschungszentrum Jülich

Subscribe to HPCwire's Weekly Update!

Be the most informed person in the room! Stay ahead of the tech trends with industry updates delivered to you every week!

Intel’s Silicon Brain System a Blueprint for Future AI Computing Architectures

April 24, 2024

Intel is releasing a whole arsenal of AI chips and systems hoping something will stick in the market. Its latest entry is a neuromorphic system called Hala Point. The system includes Intel's research chip called Loihi 2, Read more…

Anders Dam Jensen on HPC Sovereignty, Sustainability, and JU Progress

April 23, 2024

The recent 2024 EuroHPC Summit meeting took place in Antwerp, with attendance substantially up since 2023 to 750 participants. HPCwire asked Intersect360 Research senior analyst Steve Conway, who closely tracks HPC, AI, Read more…

AI Saves the Planet this Earth Day

April 22, 2024

Earth Day was originally conceived as a day of reflection. Our planet’s life-sustaining properties are unlike any other celestial body that we’ve observed, and this day of contemplation is meant to provide all of us Read more…

Intel Announces Hala Point – World’s Largest Neuromorphic System for Sustainable AI

April 22, 2024

As we find ourselves on the brink of a technological revolution, the need for efficient and sustainable computing solutions has never been more critical.  A computer system that can mimic the way humans process and s Read more…

Empowering High-Performance Computing for Artificial Intelligence

April 19, 2024

Artificial intelligence (AI) presents some of the most challenging demands in information technology, especially concerning computing power and data movement. As a result of these challenges, high-performance computing Read more…

Kathy Yelick on Post-Exascale Challenges

April 18, 2024

With the exascale era underway, the HPC community is already turning its attention to zettascale computing, the next of the 1,000-fold performance leaps that have occurred about once a decade. With this in mind, the ISC Read more…

Intel’s Silicon Brain System a Blueprint for Future AI Computing Architectures

April 24, 2024

Intel is releasing a whole arsenal of AI chips and systems hoping something will stick in the market. Its latest entry is a neuromorphic system called Hala Poin Read more…

Anders Dam Jensen on HPC Sovereignty, Sustainability, and JU Progress

April 23, 2024

The recent 2024 EuroHPC Summit meeting took place in Antwerp, with attendance substantially up since 2023 to 750 participants. HPCwire asked Intersect360 Resear Read more…

AI Saves the Planet this Earth Day

April 22, 2024

Earth Day was originally conceived as a day of reflection. Our planet’s life-sustaining properties are unlike any other celestial body that we’ve observed, Read more…

Kathy Yelick on Post-Exascale Challenges

April 18, 2024

With the exascale era underway, the HPC community is already turning its attention to zettascale computing, the next of the 1,000-fold performance leaps that ha Read more…

Software Specialist Horizon Quantum to Build First-of-a-Kind Hardware Testbed

April 18, 2024

Horizon Quantum Computing, a Singapore-based quantum software start-up, announced today it would build its own testbed of quantum computers, starting with use o Read more…

MLCommons Launches New AI Safety Benchmark Initiative

April 16, 2024

MLCommons, organizer of the popular MLPerf benchmarking exercises (training and inference), is starting a new effort to benchmark AI Safety, one of the most pre Read more…

Exciting Updates From Stanford HAI’s Seventh Annual AI Index Report

April 15, 2024

As the AI revolution marches on, it is vital to continually reassess how this technology is reshaping our world. To that end, researchers at Stanford’s Instit Read more…

Intel’s Vision Advantage: Chips Are Available Off-the-Shelf

April 11, 2024

The chip market is facing a crisis: chip development is now concentrated in the hands of the few. A confluence of events this week reminded us how few chips Read more…

Nvidia H100: Are 550,000 GPUs Enough for This Year?

August 17, 2023

The GPU Squeeze continues to place a premium on Nvidia H100 GPUs. In a recent Financial Times article, Nvidia reports that it expects to ship 550,000 of its lat Read more…

Synopsys Eats Ansys: Does HPC Get Indigestion?

February 8, 2024

Recently, it was announced that Synopsys is buying HPC tool developer Ansys. Started in Pittsburgh, Pa., in 1970 as Swanson Analysis Systems, Inc. (SASI) by John Swanson (and eventually renamed), Ansys serves the CAE (Computer Aided Engineering)/multiphysics engineering simulation market. Read more…

Intel’s Server and PC Chip Development Will Blur After 2025

January 15, 2024

Intel's dealing with much more than chip rivals breathing down its neck; it is simultaneously integrating a bevy of new technologies such as chiplets, artificia Read more…

Choosing the Right GPU for LLM Inference and Training

December 11, 2023

Accelerating the training and inference processes of deep learning models is crucial for unleashing their true potential and NVIDIA GPUs have emerged as a game- Read more…

Comparing NVIDIA A100 and NVIDIA L40S: Which GPU is Ideal for AI and Graphics-Intensive Workloads?

October 30, 2023

With long lead times for the NVIDIA H100 and A100 GPUs, many organizations are looking at the new NVIDIA L40S GPU, which it’s a new GPU optimized for AI and g Read more…

Baidu Exits Quantum, Closely Following Alibaba’s Earlier Move

January 5, 2024

Reuters reported this week that Baidu, China’s giant e-commerce and services provider, is exiting the quantum computing development arena. Reuters reported � Read more…

Shutterstock 1179408610

Google Addresses the Mysteries of Its Hypercomputer 

December 28, 2023

When Google launched its Hypercomputer earlier this month (December 2023), the first reaction was, "Say what?" It turns out that the Hypercomputer is Google's t Read more…

AMD MI3000A

How AMD May Get Across the CUDA Moat

October 5, 2023

When discussing GenAI, the term "GPU" almost always enters the conversation and the topic often moves toward performance and access. Interestingly, the word "GPU" is assumed to mean "Nvidia" products. (As an aside, the popular Nvidia hardware used in GenAI are not technically... Read more…

Leading Solution Providers

Contributors

Shutterstock 1606064203

Meta’s Zuckerberg Puts Its AI Future in the Hands of 600,000 GPUs

January 25, 2024

In under two minutes, Meta's CEO, Mark Zuckerberg, laid out the company's AI plans, which included a plan to build an artificial intelligence system with the eq Read more…

China Is All In on a RISC-V Future

January 8, 2024

The state of RISC-V in China was discussed in a recent report released by the Jamestown Foundation, a Washington, D.C.-based think tank. The report, entitled "E Read more…

Shutterstock 1285747942

AMD’s Horsepower-packed MI300X GPU Beats Nvidia’s Upcoming H200

December 7, 2023

AMD and Nvidia are locked in an AI performance battle – much like the gaming GPU performance clash the companies have waged for decades. AMD has claimed it Read more…

Nvidia’s New Blackwell GPU Can Train AI Models with Trillions of Parameters

March 18, 2024

Nvidia's latest and fastest GPU, codenamed Blackwell, is here and will underpin the company's AI plans this year. The chip offers performance improvements from Read more…

Eyes on the Quantum Prize – D-Wave Says its Time is Now

January 30, 2024

Early quantum computing pioneer D-Wave again asserted – that at least for D-Wave – the commercial quantum era has begun. Speaking at its first in-person Ana Read more…

GenAI Having Major Impact on Data Culture, Survey Says

February 21, 2024

While 2023 was the year of GenAI, the adoption rates for GenAI did not match expectations. Most organizations are continuing to invest in GenAI but are yet to Read more…

The GenAI Datacenter Squeeze Is Here

February 1, 2024

The immediate effect of the GenAI GPU Squeeze was to reduce availability, either direct purchase or cloud access, increase cost, and push demand through the roof. A secondary issue has been developing over the last several years. Even though your organization secured several racks... Read more…

Intel’s Xeon General Manager Talks about Server Chips 

January 2, 2024

Intel is talking data-center growth and is done digging graves for its dead enterprise products, including GPUs, storage, and networking products, which fell to Read more…

  • arrow
  • Click Here for More Headlines
  • arrow
HPCwire