Aug. 14, 2024 — Lawrence Livermore National Laboratory (LLNL) recently welcomed officials from the Department of Defense (DOD) and National Nuclear Security Administration (NNSA) to dedicate a new supercomputing system and Rapid Response Laboratory (RRL).

DOD is working with NNSA to significantly increase the computing capability available to the national biodefense programs. The collaboration has enabled expanding systems of the same architecture as LLNL’s upcoming exascale supercomputer, El Capitan, featuring AMD’s cutting-edge MI300A processors.

These systems will provide unique capabilities for large-scale simulation and AI-based modeling for a variety of biodefense activities, including biosurveillance, threat characterization, advanced materials development and accelerated medical countermeasures. DOD and NNSA intend to allow the U.S. government interagency, international allies and partners and academia and industry to access the supercomputing capability.

The RRL will leverage the recently dedicated supercomputing rack to enable researchers to rapidly design, test and evaluate computationally derived protein designs, in hopes of accelerating the discovery and development of medical countermeasures for emerging or unknown biological threats.

Speakers at the dual dedication highlighted the critical role of high performance computing and interagency collaboration in developing new biodefense capabilities for national security purposes. LLNL Deputy Director for Science & Technology Pat Falcone stressed the importance of collaboration between the DOD and the Tri-Labs (LLNL, Sandia National Laboratories and Los Alamos National Laboratory), and noted the significance of combining advanced computation and precision instrumentation in biodefense.

“All the labs have fancy compute, and deep roots in simulation and now in data science and artificial Intelligence approaches, and they have exquisite instrumentation, because that has been the set of responsibilities that the Department of Energy has held for the government,” Falcone said. “So, bringing that exquisite computation and precision instrumentation to the biodefense fight is really what our story is today.”

A short walk away from the computing facility, the RRL complements the DOD Chemical and Biological Defense Program’s (CBDP) Generative Unconstrained Intelligent Drug Engineering (GUIDE) program. GUIDE accelerates medical countermeasure design by leveraging machine learning-backed antibody design, experimental data, structural biology, bioinformatic modeling and molecular simulations. The program includes dozens of LLNL researchers and collaborators from government and academia, including Los Alamos and Sandia.

During the ceremony, NNSA Livermore Field Office Manager Janis Parenti acknowledged LLNL’s contributions in developing antibodies for the SARS-COV-2 virus, noting DOD’s $20 million investment in the supercomputing rack and establishment of the RRL, which “will continue to drive cutting-edge science to further enhance and strengthen our nation’s capabilities to respond to biological threats.”

Ian Watson, DOD’s deputy assistant secretary of defense for Chemical and Biological Defense, emphasized the importance of the investment to maintain competitiveness and enhance national defense capabilities.

“Exascale supercomputing and other technical enablers underscore DOD’s commitment to building enduring advantages and delivering cutting-edge defensive capabilities to ensure the Total Force can deter or prevail against advanced chemical and biological threats,” Watson said.

Advancing Biodefense Through Computation and Experimental Validation

The new computing capabilities, in conjunction with the RRL, will allow DOD and the NNSA Tri-Labs to perform rapid and iterative testing of computationally-designed vaccines and antibody drugs. The RRL will primarily support the GUIDE platform in high-throughput experimental validation of countermeasure designs.

Darryl Colvin, joint program executive officer for Chemical, Biological, Radiological, and Nuclear Defense, highlighted the RRL’s role in meeting battlefield needs for preparedness, resilience and readiness.

“Some of these medical countermeasures that we’re going to develop in this unique environment are going to be extremely important, because we’re talking about taking solutions down to days, if not hours,” Colvin said. “This computing power is going to be something that we’re going to use on a regular basis. We’re going to optimize around the things that are most important to the commanders on the ground in order for them to fight, win and survive, so we’re very excited about the opportunity.”

Andrew McIlroy, associate laboratories director for Sandia/California, discussed Sandia’s expertise in virology and high-throughput experimentation, and emphasized the need for a strong link between computation and lab experiments.

“For traditional computation, we need validation data — that’s extremely important for some of the advanced methods. We’re starting to use artificial intelligence and machine learning, and you need fast and reliable datasets to apply those techniques. That’s where the high throughput computation or high throughput experimental capabilities that are being developed here at Lawrence Livermore are incredibly important to create the synergy between the computation and the experimentation.”

LANL’s Acting Bioscience Division Leader Kirsten McCabe expressed enthusiasm for integrating computational and experimental efforts at LANL, and the potential for the RRL to expand those partnerships.

“We’re really focused on making sure that we’re working in safety and security and adding that security layer to everything that we’re doing. I think the Tri-Labs are really coming together as a family. We have seen such building of bridges in everything from our internal funding efforts to virus surveillance and medical countermeasures; it’s really been an exciting time to see how that we can work together. We’ve been waiting so long for this long-term vision for bio, and it’s here. I find that so exciting.”

Rapid Response Through Experimental Automation

Managed by LLNL staff scientist Edwin Saada, the RRL features molecular and characterization rooms equipped with automated robotics and advanced machines. These facilities will enable high-throughput experiments on re-engineered proteins and countermeasure candidates simultaneously, significantly accelerating the initial phase of drug discovery.

“The analogy I use is that it’s like optimizing the gears in a machine,” Saada said. “If you want more benefit out of the computation, you either increase speed or force. In our case, computation is the big gear with immense power. However, our biological capabilities were not at the same level. So, we needed to pause and say, ‘Alright, let’s figure this out. Let’s get to generating large amounts of data, and feeding this back into computation so we can get an iterative process going.’ Our goal was to make biology a bigger and more efficient gear, so that when partnered with computation we work together and make the whole GUIDE system bigger, stronger and faster.”

LLNL’s Deputy Associate Director for Computing Jim Brase emphasized the transformative potential of integrating lab work with large-scale HPC facilities. This approach combines computational and experimental data to improve predictive modeling, allowing for rapid threat detection and response.

“The ability to put in these new platform capabilities, to gather bigger and more extensive computing — and to have a closely connected laboratory that can take those computational results, make molecules and then test them against biological targets that rapidly feed that back to the computing — allows us to go faster and have better performance,” Brase said. “That’s really the key to transforming our ability to detect threats, to assess how serious they are and to respond in the timescales that we need for countermeasures. This isn’t about one project, or one particular biothreat or chemical agent, this is about building this broad national capability, so that no matter what comes up or what we see coming down the road, we can rapidly assess and respond to it.”

More information on GUIDE and ongoing biodefense efforts at LLNL can be found here.

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Source: LLNL