Supercomputers Help ORNL Researchers Identify Key Molecular Switch

December 17, 2013

OAK RIDGE, Tenn., Dec. 17 — If scientists can control cellular functions such as movement and development, they can cripple cells and pathogens that are causing disease in the body.Supported by National Institutes of Health grants, researchers at Oak Ridge National Laboratory (ORNL), the University of Tennessee (UT), and the UT-ORNL Joint Institute for Computational Sciences (JICS) discovered a molecular “switch” in a receptor that controls cell behavior using detailed molecular dynamics simulations on a computer called Anton built by D. E. Shaw Research in New York City. To study an even larger signaling complex surrounding the switch, the team is expanding these simulations on the 27-petaflop, CPU-GPU machine Titan-the nation’s most powerful supercomputer, managed by the Oak Ridge Leadership Computing Facility at ORNL.

Researchers identified the molecular switch on Anton (which was designed to perform speedy molecular dynamics simulations) by simulating 140,000 atoms that make up the signaling part of the Tsr chemoreceptor that controls motility in E. coli. Like other receptors, Tsr spans the cell membrane, communicating to proteins inside the cell in order to respond to threats or opportunities in the environment.

The results, published in Nature Communications, stand apart from previous research because of the computational power applied to the problem.

“This work exemplifies the growing importance of numerical experiments in biology,” said Jerome Baudry, assistant professor in the UT Biochemistry and Cellular and Molecular Biology Department and the UT-ORNL Center for Molecular Biophysics.

The team led by Baudry and Igor Zhulin, distinguished research and development staff member in the ORNL Computer Science and Mathematics Division, joint professor in the UT Department of Microbiology, and JICS joint faculty member determined that a single pair of phenylalanine amino acids called Phe396 located at the chemoreceptor tip was acting as a receptor switch.

“For decades proteins have been viewed as static molecules, and almost everything we know about them comes from static images, such as those produced with X-ray crystallography,” Zhulin said. “But signaling is a dynamic process, which is difficult to fully understand using only snapshots.”

The Phe396 pair is restless, always flipping 180 degrees back and forth relative to the receptor, but researchers identified a clear pattern.

“It is like a crazy light switch,” Zhulin said. “When you switch it on to light up your room, it occasionally flips down giving you moments of darkness, and when you switch it off to go to sleep, it occasionally goes up flashing.”When the receptor is in signal-on mode, the switch spends more time in the “on” position. When the receptor is in signal-off mode, the switch spends more time in the “off” position.

“To our knowledge, this is the first time this switch has been described,” said Davi Ortega, lead author and postdoctoral fellow in Zhulin’s lab. The team, including collaborators at the University of Utah led by John Parkinson, compared thousands of chemoreceptor sequences from all microbial genomes in the Microbial Signal Transduction database available as of August 2012. Remarkably, the Phe396 amino acid was present in all of them, indicating it is likely the switch has existed throughout more than 2 billion years of microbial evolution. Phenylalanine pairs capable of forming a molecular switch are also present in many other signaling proteins, including receptors in human cells, making it an attractive target for drug design and biotechnology applications.

However, using Anton, researchers were able to simulate only a small part of the chemoreceptor containing the Phe396 pair known as a dimer, meaning two identical molecules. But these two molecules do not work alone.

Dimers are grouped in threes to form larger units of the signaling complex, called trimers of dimers. Researchers expect simulating a trimer next will reveal more about how the Phe396-mediated signal is amplified across neighboring proteins.

But a trimer simulation requires modeling almost 400,000 atoms with increasingly complex physics calculations as the system gets larger. To do so, the group needs a lot of computational capacity.

“Anton is an exceptional machine, but its hardware limitations won’t permit the simulation of such a large system,” Ortega said. “We need Titan.”

Using Titan they ran a preliminary simulation to determine that they would need millions of processing hours on this petaflop machine capable of quadrillions of calculations per second. Titan’s GPUs are highly parallel, hurtling through repetitive calculations such as those modeling the large system of atoms under a vast array of configurations in the trimer simulation.

“With Titan we will begin to see how the signal propagates across chemoreceptors,” Zhulin said. “We think this will start to explain how signals are amplified by these remarkable molecular machines.”ORNL is managed by UT-Battelle for the Department of Energy’s Office of Science. DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, please visit http://science.energy.gov.

—–

Source: ORNL

Subscribe to HPCwire's Weekly Update!

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

Graphcore Readies Launch of 16nm Colossus-IPU Chip

July 20, 2017

A second $30 million funding round for U.K. AI chip developer Graphcore sets up the company to go to market with its “intelligent processing unit” (IPU) in 2017 with scale-up production for enterprise datacenters and Read more…

By Tiffany Trader

Fine-Tuning Severe Hail Forecasting with Machine Learning

July 20, 2017

Depending on whether you’ve been caught outside during a severe hail storm, the sight of greenish tinted clouds on the horizon may cause serious knots in the pit of your stomach, or at least give you pause. There’s g Read more…

By Sean Thielen

Trinity Supercomputer’s Haswell and KNL Partitions Are Merged

July 19, 2017

Trinity supercomputer’s two partitions – one based on Intel Xeon Haswell processors and the other on Xeon Phi Knights Landing – have been fully integrated are now available for use on classified work in the Nationa Read more…

By HPCwire Staff

Fujitsu Continues HPC, AI Push

July 19, 2017

Summer is well under way, but the so-called summertime slowdown, linked with hot temperatures and longer vacations, does not seem to have impacted Fujitsu's output. The Japanese multinational has made a raft of HPC and A Read more…

By Tiffany Trader

HPE Extreme Performance Solutions

HPE Servers Deliver High Performance Remote Visualization

Whether generating seismic simulations, locating new productive oil reservoirs, or constructing complex models of the earth’s subsurface, energy, oil, and gas (EO&G) is a highly data-driven industry. Read more…

Researchers Use DNA to Store and Retrieve Digital Movie

July 18, 2017

From abacus to pencil and paper to semiconductor chips, the technology of computing has always been an ever-changing target. The human brain is probably the computer we use most (hopefully) and understand least. This mon Read more…

By John Russell

The Exascale FY18 Budget – The Next Step

July 17, 2017

On July 12, 2017, the U.S. federal budget for its Exascale Computing Initiative (ECI) took its next step forward. On that day, the full Appropriations Committee of the House of Representatives voted to accept the recomme Read more…

By Alex R. Larzelere

Summer Reading: IEEE Spectrum’s Chip Hall of Fame

July 17, 2017

Take a trip down memory lane – the Mostek MK4096 4-kilobit DRAM, for instance. Perhaps processors are more to your liking. Remember the Sh-Boom processor (1988), created by Russell Fish and Chuck Moore, and named after Read more…

By John Russell

Women in HPC Luncheon Shines Light on Female-Friendly Hiring Practices

July 13, 2017

The second annual Women in HPC luncheon was held on June 20, 2017, during the International Supercomputing Conference in Frankfurt, Germany. The luncheon provides participants the opportunity to network with industry lea Read more…

By Tiffany Trader

Graphcore Readies Launch of 16nm Colossus-IPU Chip

July 20, 2017

A second $30 million funding round for U.K. AI chip developer Graphcore sets up the company to go to market with its “intelligent processing unit” (IPU) in Read more…

By Tiffany Trader

Fine-Tuning Severe Hail Forecasting with Machine Learning

July 20, 2017

Depending on whether you’ve been caught outside during a severe hail storm, the sight of greenish tinted clouds on the horizon may cause serious knots in the Read more…

By Sean Thielen

Fujitsu Continues HPC, AI Push

July 19, 2017

Summer is well under way, but the so-called summertime slowdown, linked with hot temperatures and longer vacations, does not seem to have impacted Fujitsu's out Read more…

By Tiffany Trader

Researchers Use DNA to Store and Retrieve Digital Movie

July 18, 2017

From abacus to pencil and paper to semiconductor chips, the technology of computing has always been an ever-changing target. The human brain is probably the com Read more…

By John Russell

The Exascale FY18 Budget – The Next Step

July 17, 2017

On July 12, 2017, the U.S. federal budget for its Exascale Computing Initiative (ECI) took its next step forward. On that day, the full Appropriations Committee Read more…

By Alex R. Larzelere

Women in HPC Luncheon Shines Light on Female-Friendly Hiring Practices

July 13, 2017

The second annual Women in HPC luncheon was held on June 20, 2017, during the International Supercomputing Conference in Frankfurt, Germany. The luncheon provid Read more…

By Tiffany Trader

Satellite Advances, NSF Computation Power Rapid Mapping of Earth’s Surface

July 13, 2017

New satellite technologies have completely changed the game in mapping and geographical data gathering, reducing costs and placing a new emphasis on time series Read more…

By Ken Chiacchia and Tiffany Jolley

Intel Skylake: Xeon Goes from Chip to Platform

July 13, 2017

With yesterday’s New York unveiling of the new “Skylake” Xeon Scalable processors, Intel made multiple runs at multiple competitive threats and strategic Read more…

By Doug Black

Google Pulls Back the Covers on Its First Machine Learning Chip

April 6, 2017

This week Google released a report detailing the design and performance characteristics of the Tensor Processing Unit (TPU), its custom ASIC for the inference Read more…

By Tiffany Trader

Nvidia Responds to Google TPU Benchmarking

April 10, 2017

Nvidia highlights strengths of its newest GPU silicon in response to Google's report on the performance and energy advantages of its custom tensor processor. Read more…

By Tiffany Trader

Quantum Bits: D-Wave and VW; Google Quantum Lab; IBM Expands Access

March 21, 2017

For a technology that’s usually characterized as far off and in a distant galaxy, quantum computing has been steadily picking up steam. Just how close real-wo Read more…

By John Russell

HPC Compiler Company PathScale Seeks Life Raft

March 23, 2017

HPCwire has learned that HPC compiler company PathScale has fallen on difficult times and is asking the community for help or actively seeking a buyer for its a Read more…

By Tiffany Trader

Trump Budget Targets NIH, DOE, and EPA; No Mention of NSF

March 16, 2017

President Trump’s proposed U.S. fiscal 2018 budget issued today sharply cuts science spending while bolstering military spending as he promised during the cam Read more…

By John Russell

CPU-based Visualization Positions for Exascale Supercomputing

March 16, 2017

In this contributed perspective piece, Intel’s Jim Jeffers makes the case that CPU-based visualization is now widely adopted and as such is no longer a contrarian view, but is rather an exascale requirement. Read more…

By Jim Jeffers, Principal Engineer and Engineering Leader, Intel

Nvidia’s Mammoth Volta GPU Aims High for AI, HPC

May 10, 2017

At Nvidia's GPU Technology Conference (GTC17) in San Jose, Calif., this morning, CEO Jensen Huang announced the company's much-anticipated Volta architecture a Read more…

By Tiffany Trader

Facebook Open Sources Caffe2; Nvidia, Intel Rush to Optimize

April 18, 2017

From its F8 developer conference in San Jose, Calif., today, Facebook announced Caffe2, a new open-source, cross-platform framework for deep learning. Caffe2 is the successor to Caffe, the deep learning framework developed by Berkeley AI Research and community contributors. Read more…

By Tiffany Trader

Leading Solution Providers

How ‘Knights Mill’ Gets Its Deep Learning Flops

June 22, 2017

Intel, the subject of much speculation regarding the delayed, rewritten or potentially canceled “Aurora” contract (the Argonne Lab part of the CORAL “ Read more…

By Tiffany Trader

Reinders: “AVX-512 May Be a Hidden Gem” in Intel Xeon Scalable Processors

June 29, 2017

Imagine if we could use vector processing on something other than just floating point problems.  Today, GPUs and CPUs work tirelessly to accelerate algorithms Read more…

By James Reinders

MIT Mathematician Spins Up 220,000-Core Google Compute Cluster

April 21, 2017

On Thursday, Google announced that MIT math professor and computational number theorist Andrew V. Sutherland had set a record for the largest Google Compute Engine (GCE) job. Sutherland ran the massive mathematics workload on 220,000 GCE cores using preemptible virtual machine instances. Read more…

By Tiffany Trader

Russian Researchers Claim First Quantum-Safe Blockchain

May 25, 2017

The Russian Quantum Center today announced it has overcome the threat of quantum cryptography by creating the first quantum-safe blockchain, securing cryptocurrencies like Bitcoin, along with classified government communications and other sensitive digital transfers. Read more…

By Doug Black

Google Debuts TPU v2 and will Add to Google Cloud

May 25, 2017

Not long after stirring attention in the deep learning/AI community by revealing the details of its Tensor Processing Unit (TPU), Google last week announced the Read more…

By John Russell

Groq This: New AI Chips to Give GPUs a Run for Deep Learning Money

April 24, 2017

CPUs and GPUs, move over. Thanks to recent revelations surrounding Google’s new Tensor Processing Unit (TPU), the computing world appears to be on the cusp of Read more…

By Alex Woodie

Six Exascale PathForward Vendors Selected; DoE Providing $258M

June 15, 2017

The much-anticipated PathForward awards for hardware R&D in support of the Exascale Computing Project were announced today with six vendors selected – AMD Read more…

By John Russell

Top500 Results: Latest List Trends and What’s in Store

June 19, 2017

Greetings from Frankfurt and the 2017 International Supercomputing Conference where the latest Top500 list has just been revealed. Although there were no major Read more…

By Tiffany Trader

  • arrow
  • Click Here for More Headlines
  • arrow
Share This