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!

Scalable Informatics Ceases Operations

March 23, 2017

On the same day we reported on the uncertain future for HPC compiler company PathScale, we are sad to learn that another HPC vendor, Scalable Informatics, is closing its doors. Read more…

By Tiffany Trader

‘Strategies in Biomedical Data Science’ Advances IT-Research Synergies

March 23, 2017

“Strategies in Biomedical Data Science: Driving Force for Innovation” by Jay A. Etchings is both an introductory text and a field guide for anyone working with biomedical data. Read more…

By Tiffany Trader

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 assets. Read more…

By Tiffany Trader

Google Launches New Machine Learning Journal

March 22, 2017

On Monday, Google announced plans to launch a new peer review journal and “ecosystem” Read more…

By John Russell

HPE Extreme Performance Solutions

HFT Firms Turn to Co-Location to Gain Competitive Advantage

High-frequency trading (HFT) is a high-speed, high-stakes world where every millisecond matters. Finding ways to execute trades faster than the competition translates directly to greater revenue for firms, brokerages, and exchanges. Read more…

Swiss Researchers Peer Inside Chips with Improved X-Ray Imaging

March 22, 2017

Peering inside semiconductor chips using x-ray imaging isn’t new, but the technique hasn’t been especially good or easy to accomplish. Read more…

By John Russell

LANL Simulation Shows Massive Black Holes Break ‘Speed Limit’

March 21, 2017

A new computer simulation based on codes developed at Los Alamos National Laboratory (LANL) is shedding light on how supermassive black holes could have formed in the early universe contrary to most prior models which impose a limit on how fast these massive ‘objects’ can form. Read more…

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. Read more…

By John Russell

Intel Ships Drives Based on 3D XPoint Non-volatile Memory

March 20, 2017

Intel Corp. has begun shipping new storage drives based on its 3D XPoint non-volatile memory technology as it targets data-driven workloads. Intel’s new Optane solid-state drives, designated P4800X, seek to combine the attributes of memory and storage in the same device. Read more…

By George Leopold

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 assets. 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. Read more…

By John Russell

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 campaign. 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

US Supercomputing Leaders Tackle the China Question

March 15, 2017

Joint DOE-NSA report responds to the increased global pressures impacting the competitiveness of U.S. supercomputing. Read more…

By Tiffany Trader

New Japanese Supercomputing Project Targets Exascale

March 14, 2017

Another Japanese supercomputing project was revealed this week, this one from emerging supercomputer maker, ExaScaler Inc., and Keio University. The partners are working on an original supercomputer design with exascale aspirations. Read more…

By Tiffany Trader

Nvidia Debuts HGX-1 for Cloud; Announces Fujitsu AI Deal

March 9, 2017

On Monday Nvidia announced a major deal with Fujitsu to help build an AI supercomputer for RIKEN using 24 DGX-1 servers. Read more…

By John Russell

HPC4Mfg Advances State-of-the-Art for American Manufacturing

March 9, 2017

Last Friday (March 3, 2017), the High Performance Computing for Manufacturing (HPC4Mfg) program held an industry engagement day workshop in San Diego, bringing together members of the US manufacturing community, national laboratories and universities to discuss the role of high-performance computing as an innovation engine for American manufacturing. Read more…

By Tiffany Trader

For IBM/OpenPOWER: Success in 2017 = (Volume) Sales

January 11, 2017

To a large degree IBM and the OpenPOWER Foundation have done what they said they would – assembling a substantial and growing ecosystem and bringing Power-based products to market, all in about three years. Read more…

By John Russell

TSUBAME3.0 Points to Future HPE Pascal-NVLink-OPA Server

February 17, 2017

Since our initial coverage of the TSUBAME3.0 supercomputer yesterday, more details have come to light on this innovative project. Of particular interest is a new board design for NVLink-equipped Pascal P100 GPUs that will create another entrant to the space currently occupied by Nvidia's DGX-1 system, IBM's "Minsky" platform and the Supermicro SuperServer (1028GQ-TXR). Read more…

By Tiffany Trader

Tokyo Tech’s TSUBAME3.0 Will Be First HPE-SGI Super

February 16, 2017

In a press event Friday afternoon local time in Japan, Tokyo Institute of Technology (Tokyo Tech) announced its plans for the TSUBAME3.0 supercomputer, which will be Japan’s “fastest AI supercomputer,” Read more…

By Tiffany Trader

IBM Wants to be “Red Hat” of Deep Learning

January 26, 2017

IBM today announced the addition of TensorFlow and Chainer deep learning frameworks to its PowerAI suite of deep learning tools, which already includes popular offerings such as Caffe, Theano, and Torch. Read more…

By John Russell

Lighting up Aurora: Behind the Scenes at the Creation of the DOE’s Upcoming 200 Petaflops Supercomputer

December 1, 2016

In April 2015, U.S. Department of Energy Undersecretary Franklin Orr announced that Intel would be the prime contractor for Aurora: Read more…

By Jan Rowell

Is Liquid Cooling Ready to Go Mainstream?

February 13, 2017

Lost in the frenzy of SC16 was a substantial rise in the number of vendors showing server oriented liquid cooling technologies. Three decades ago liquid cooling was pretty much the exclusive realm of the Cray-2 and IBM mainframe class products. That’s changing. We are now seeing an emergence of x86 class server products with exotic plumbing technology ranging from Direct-to-Chip to servers and storage completely immersed in a dielectric fluid. Read more…

By Steve Campbell

Enlisting Deep Learning in the War on Cancer

December 7, 2016

Sometime in Q2 2017 the first ‘results’ of the Joint Design of Advanced Computing Solutions for Cancer (JDACS4C) will become publicly available according to Rick Stevens. He leads one of three JDACS4C pilot projects pressing deep learning (DL) into service in the War on Cancer. Read more…

By John Russell

BioTeam’s Berman Charts 2017 HPC Trends in Life Sciences

January 4, 2017

Twenty years ago high performance computing was nearly absent from life sciences. Today it’s used throughout life sciences and biomedical research. Genomics and the data deluge from modern lab instruments are the main drivers, but so is the longer-term desire to perform predictive simulation in support of Precision Medicine (PM). There’s even a specialized life sciences supercomputer, ‘Anton’ from D.E. Shaw Research, and the Pittsburgh Supercomputing Center is standing up its second Anton 2 and actively soliciting project proposals. There’s a lot going on. Read more…

By John Russell

Leading Solution Providers

HPC Startup Advances Auto-Parallelization’s Promise

January 23, 2017

The shift from single core to multicore hardware has made finding parallelism in codes more important than ever, but that hasn’t made the task of parallel programming any easier. Read more…

By Tiffany Trader

HPC Technique Propels Deep Learning at Scale

February 21, 2017

Researchers from Baidu’s Silicon Valley AI Lab (SVAIL) have adapted a well-known HPC communication technique to boost the speed and scale of their neural network training and now they are sharing their implementation with the larger deep learning community. Read more…

By Tiffany Trader

CPU Benchmarking: Haswell Versus POWER8

June 2, 2015

With OpenPOWER activity ramping up and IBM’s prominent role in the upcoming DOE machines Summit and Sierra, it’s a good time to look at how the IBM POWER CPU stacks up against the x86 Xeon Haswell CPU from Intel. 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 campaign. Read more…

By John Russell

IDG to Be Bought by Chinese Investors; IDC to Spin Out HPC Group

January 19, 2017

US-based publishing and investment firm International Data Group, Inc. (IDG) will be acquired by a pair of Chinese investors, China Oceanwide Holdings Group Co., Ltd. Read more…

By Tiffany Trader

US Supercomputing Leaders Tackle the China Question

March 15, 2017

Joint DOE-NSA report responds to the increased global pressures impacting the competitiveness of U.S. supercomputing. 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. Read more…

By John Russell

Intel and Trump Announce $7B for Fab 42 Targeting 7nm

February 8, 2017

In what may be an attempt by President Trump to reset his turbulent relationship with the high tech industry, he and Intel CEO Brian Krzanich today announced plans to invest more than $7 billion to complete Fab 42. Read more…

By John Russell

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