Blue Waters Helps Beckman Researchers Construct Atomic Model of an Immature Retrovirus

August 12, 2015

Aug. 12 — Using molecular modeling and large-scale molecular dynamic simulation, Beckman researchers have constructed an atomic model of an immature retrovirus.

The researchers from the Theoretical and Computational Biophysics Group published their work in the journal Structure.

Retroviruses, such as HIV, are tricky to treat. They go through a multistage process to produce infectious particles. The viruses that are released from infected cells are initially in an immature state and are composed of an RNA genome surrounded by a coat of protein. Upon their release, the viruses undergo a maturation process that rearranges the viral proteins and activates the conversion of the RNA genome into DNA through a process called reverse transcription. The viral DNA then invades the host cell’s genome. The infected cell is programmed to release multiple copies of the immature virus into the host’s bloodstream. These newly released viruses must in turn mature before they can infect other cells.

Not only do retroviruses cause life-long infections, but also in the complex process of reverse-transcribing RNA into DNA, many mutations can occur, making the retrovirus even more difficult to target.

One strategy for preventing the spread of a retrovirus is to lock the viral particles in their immature, non-infectious state. Unfortunately, the complexity and size of the viral particle―an irregular and incomplete hexagonal shell of close to 100 nanometers in size―have prevented the experimental determination of the atomic-level structure of the particle.

A number of studies have examined the structure of the Rous sarcoma virus (RSV), which affects birds and provides a good model for other retroviruses, but none have been able to provide a high-resolution look at the immature stage of the virus.

Over a period of two years, researchers have been performing calculations and simulations in order to reveal the structural features of the virus. With the help of the Titan supercomputer at the Oak Ridge Leadership Computing Facility in Tennessee and the Blue Waters supercomputer at the National Center for Supercomputing Applications (NCSA) at Illinois, the researchers were the first to provide the atomic-level structural model of the immature retroviral lattice of RSV. A five-microsecond simulation describing the motion of half a million atoms involves a hefty calculation that took five days using 30 percent of the Titan supercomputer, more than 5,000 computing nodes—each node is equivalent to a high-end workstation.

“We have had a pretty good understanding of the mature infectious particle at a level where we can make specific predictions about the local chemical interactions between the protein subunits in the virus,” said Rebecca Craven, professor of microbiology and immunology and at Penn State University and one of the study’s authors. “But the field was really lacking similar high-resolution knowledge about the immature virus. This new model is the first to give us an atomic-level look at the immature state. With that knowledge we can try to understand the precise molecular mechanisms of virus maturation and help to elucidate how drugs can be designed to interfere with that.”

According to Boon Chong Goh, a graduate student in physics at Illinois and lead author on the study, a six-helix bundle domain located on the inside surface of the immature protein shell could be a key to understanding and blocking the virus.

“Recent advances in cryo-electron tomography allow us to model the majority of the immature retroviral lattice, except the six-helix bundle domain,” said Goh. “Experimentalists do not have a clear view of that domain because of its high flexibility. And that’s where we come in. Using advanced computational techniques and supercomputers, we modeled and refined an all-atom model of the six-helix bundle.

The researchers believe that the six-helix bundle is amphipathic, a chemical property that possesses an affinity for both water and fat, and that it is enclosed by a ring of salt bridges, contributing to the stability of the bundle.

“HIV is a close relative to RSV, and HIV is also known to have this domain, which has been a drug target for years. A drug named Bevirimat (BVM) was developed to target the six-helix bundle of immature HIV, but it did not pass the clinical trials,” said Goh.

“The experience with BVM did show that inhibitors that target the six helix bundle domain can be very powerful HIV anti-retroviral drugs by preventing virus maturation,” said Craven.

“The main idea is that you have two forms of the virus: the immature and the mature,” said Juan Perilla, postdoctoral researcher and co-first author of the study. “The immature is not infectious, so the idea is that ultimately you want to prevent it from becoming the mature form. The problem is that BVM targets the six-helix bundle domain, but no one really knows the structure of the immature lattice in HIV. There are a few models, but they are not high resolution, so we decided to work in this direction and we picked RSV because it’s a good model to study the virus. Our next step is to go to HIV.”

“This result is an example of where computational methodology is really complementing medical lab experiments,” said Klaus Schulten, director of the TCBG and professor of physics.

According to Schulten, computational experiments can help provide solutions to complex problems in the laboratory.

“The living world is made of molecules and you need to know this world. Sometimes you just do it through trial and error in a chemical research lab and you see that a newly designed drug molecule has a certain effect that often you only understand later. But then there is, of course, a more systematic way of resolving the molecular world, namely the computational way taken in our RSV study, and one can derive medical treatments from the knowledge reached computationally,” Schulten explained. “This will be done more and more often.”

The group has already begun the process of studying the immature HIV virus on the Blue Waters supercomputer located at the National Center for Supercomputing Applications at Illinois.

Source: Beckman Institute, University of Illinois at Urbana-Champaign

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!

Digging into the Atos-Nimbix Deal: Big US HPC and Global Cloud Aspirations. Look out HPE?

August 2, 2021

Behind Atos’s deal announced last week to acquire HPC-cloud specialist Nimbix are ramped-up plans to penetrate the U.S. HPC market and global expansion of its HPC cloud capabilities. Nimbix will become “an Atos HPC c Read more…

Berkeley Lab Makes Strides in Autonomous Discovery to Tackle the Data Deluge

August 2, 2021

Data production is outpacing the human capacity to process said data. Whether a giant radio telescope, a new particle accelerator or lidar data from autonomous cars, the sheer scale of the data generated is increasingly Read more…

Verifying the Universe with Exascale Computers

July 30, 2021

The ExaSky project, one of the critical Earth and Space Science applications being solved by the US Department of Energy’s (DOE’s) Exascale Computing Project (ECP), is preparing to use the nation’s forthcoming exas Read more…

What’s After Exascale? The Internet of Workflows Says HPE’s Nicolas Dubé

July 29, 2021

With the race to exascale computing in its final leg, it’s natural to wonder what the Post Exascale Era will look like. Nicolas Dubé, VP and chief technologist for HPE’s HPC business unit, agrees and shared his vision at Supercomputing Frontiers Europe 2021 held last week. The next big thing, he told the virtual audience at SFE21, is something that will connect HPC and (broadly) all of IT – into what Dubé calls The Internet of Workflows. Read more…

How UK Scientists Developed Transformative, HPC-Powered Coronavirus Sequencing System

July 29, 2021

In November 2020, the COVID-19 Genomics UK Consortium (COG-UK) won the HPCwire Readers’ Choice Award for Best HPC Collaboration for its CLIMB-COVID sequencing project. Launched in March 2020, CLIMB-COVID has now resulted in the sequencing of over 675,000 coronavirus genomes – an increasingly critical task as variants like Delta threaten the tenuous prospect of a return to normalcy in much of the world. Read more…

AWS Solution Channel

Data compression with increased performance and lower costs

Many customers associate a performance cost with data compression, but that’s not the case with Amazon FSx for Lustre. With FSx for Lustre, data compression reduces storage costs and increases aggregate file system throughput. Read more…

KAUST Leverages Mixed Precision for Geospatial Data

July 28, 2021

For many computationally intensive tasks, exacting precision is not necessary for every step of the entire task to obtain a suitably precise result. The alternative is mixed-precision computing: using high precision wher Read more…

Digging into the Atos-Nimbix Deal: Big US HPC and Global Cloud Aspirations. Look out HPE?

August 2, 2021

Behind Atos’s deal announced last week to acquire HPC-cloud specialist Nimbix are ramped-up plans to penetrate the U.S. HPC market and global expansion of its Read more…

How UK Scientists Developed Transformative, HPC-Powered Coronavirus Sequencing System

July 29, 2021

In November 2020, the COVID-19 Genomics UK Consortium (COG-UK) won the HPCwire Readers’ Choice Award for Best HPC Collaboration for its CLIMB-COVID sequencing project. Launched in March 2020, CLIMB-COVID has now resulted in the sequencing of over 675,000 coronavirus genomes – an increasingly critical task as variants like Delta threaten the tenuous prospect of a return to normalcy in much of the world. Read more…

What’s After Exascale? The Internet of Workflows Says HPE’s Nicolas Dubé

July 29, 2021

With the race to exascale computing in its final leg, it’s natural to wonder what the Post Exascale Era will look like. Nicolas Dubé, VP and chief technologist for HPE’s HPC business unit, agrees and shared his vision at Supercomputing Frontiers Europe 2021 held last week. The next big thing, he told the virtual audience at SFE21, is something that will connect HPC and (broadly) all of IT – into what Dubé calls The Internet of Workflows. Read more…

IBM and University of Tokyo Roll Out Quantum System One in Japan

July 27, 2021

IBM and the University of Tokyo today unveiled an IBM Quantum System One as part of the IBM-Japan quantum program announced in 2019. The system is the second IB Read more…

Intel Unveils New Node Names; Sapphire Rapids Is Now an ‘Intel 7’ CPU

July 27, 2021

What's a preeminent chip company to do when its process node technology lags the competition by (roughly) one generation, but outmoded naming conventions make it seem like it's two nodes behind? For Intel, the response was to change how it refers to its nodes with the aim of better reflecting its positioning within the leadership semiconductor manufacturing space. Intel revealed its new node nomenclature, and... Read more…

Will Approximation Drive Post-Moore’s Law HPC Gains?

July 26, 2021

“Hardware-based improvements are going to get more and more difficult,” said Neil Thompson, an innovation scholar at MIT’s Computer Science and Artificial Intelligence Lab (CSAIL). “I think that’s something that this crowd will probably, actually, be already familiar with.” Thompson, speaking... Read more…

With New Owner and New Roadmap, an Independent Omni-Path Is Staging a Comeback

July 23, 2021

Put on a shelf by Intel in 2019, Omni-Path faced a uncertain future, but under new custodian Cornelis Networks, OmniPath is looking to make a comeback as an independent high-performance interconnect solution. A "significant refresh" – called Omni-Path Express – is coming later this year according to the company. Cornelis Networks formed last September as a spinout of Intel's Omni-Path division. Read more…

Chameleon’s HPC Testbed Sharpens Its Edge, Presses ‘Replay’

July 22, 2021

“One way of saying what I do for a living is to say that I develop scientific instruments,” said Kate Keahey, a senior fellow at the University of Chicago a Read more…

AMD Chipmaker TSMC to Use AMD Chips for Chipmaking

May 8, 2021

TSMC has tapped AMD to support its major manufacturing and R&D workloads. AMD will provide its Epyc Rome 7702P CPUs – with 64 cores operating at a base cl Read more…

Intel Launches 10nm ‘Ice Lake’ Datacenter CPU with Up to 40 Cores

April 6, 2021

The wait is over. Today Intel officially launched its 10nm datacenter CPU, the third-generation Intel Xeon Scalable processor, codenamed Ice Lake. With up to 40 Read more…

Berkeley Lab Debuts Perlmutter, World’s Fastest AI Supercomputer

May 27, 2021

A ribbon-cutting ceremony held virtually at Berkeley Lab's National Energy Research Scientific Computing Center (NERSC) today marked the official launch of Perlmutter – aka NERSC-9 – the GPU-accelerated supercomputer built by HPE in partnership with Nvidia and AMD. Read more…

Ahead of ‘Dojo,’ Tesla Reveals Its Massive Precursor Supercomputer

June 22, 2021

In spring 2019, Tesla made cryptic reference to a project called Dojo, a “super-powerful training computer” for video data processing. Then, in summer 2020, Tesla CEO Elon Musk tweeted: “Tesla is developing a [neural network] training computer called Dojo to process truly vast amounts of video data. It’s a beast! … A truly useful exaflop at de facto FP32.” Read more…

Google Launches TPU v4 AI Chips

May 20, 2021

Google CEO Sundar Pichai spoke for only one minute and 42 seconds about the company’s latest TPU v4 Tensor Processing Units during his keynote at the Google I Read more…

CentOS Replacement Rocky Linux Is Now in GA and Under Independent Control

June 21, 2021

The Rocky Enterprise Software Foundation (RESF) is announcing the general availability of Rocky Linux, release 8.4, designed as a drop-in replacement for the soon-to-be discontinued CentOS. The GA release is launching six-and-a-half months after Red Hat deprecated its support for the widely popular, free CentOS server operating system. The Rocky Linux development effort... Read more…

Iran Gains HPC Capabilities with Launch of ‘Simorgh’ Supercomputer

May 18, 2021

Iran is said to be developing domestic supercomputing technology to advance the processing of scientific, economic, political and military data, and to strengthen the nation’s position in the age of AI and big data. On Sunday, Iran unveiled the Simorgh supercomputer, which will deliver.... Read more…

HPE Launches Storage Line Loaded with IBM’s Spectrum Scale File System

April 6, 2021

HPE today launched a new family of storage solutions bundled with IBM’s Spectrum Scale Erasure Code Edition parallel file system (description below) and featu Read more…

Leading Solution Providers

Contributors

10nm, 7nm, 5nm…. Should the Chip Nanometer Metric Be Replaced?

June 1, 2020

The biggest cool factor in server chips is the nanometer. AMD beating Intel to a CPU built on a 7nm process node* – with 5nm and 3nm on the way – has been i Read more…

Julia Update: Adoption Keeps Climbing; Is It a Python Challenger?

January 13, 2021

The rapid adoption of Julia, the open source, high level programing language with roots at MIT, shows no sign of slowing according to data from Julialang.org. I Read more…

GTC21: Nvidia Launches cuQuantum; Dips a Toe in Quantum Computing

April 13, 2021

Yesterday Nvidia officially dipped a toe into quantum computing with the launch of cuQuantum SDK, a development platform for simulating quantum circuits on GPU-accelerated systems. As Nvidia CEO Jensen Huang emphasized in his keynote, Nvidia doesn’t plan to build... Read more…

Microsoft to Provide World’s Most Powerful Weather & Climate Supercomputer for UK’s Met Office

April 22, 2021

More than 14 months ago, the UK government announced plans to invest £1.2 billion ($1.56 billion) into weather and climate supercomputing, including procuremen Read more…

Quantum Roundup: IBM, Rigetti, Phasecraft, Oxford QC, China, and More

July 13, 2021

IBM yesterday announced a proof for a quantum ML algorithm. A week ago, it unveiled a new topology for its quantum processors. Last Friday, the Technical Univer Read more…

AMD-Xilinx Deal Gains UK, EU Approvals — China’s Decision Still Pending

July 1, 2021

AMD’s planned acquisition of FPGA maker Xilinx is now in the hands of Chinese regulators after needed antitrust approvals for the $35 billion deal were receiv Read more…

Q&A with Jim Keller, CTO of Tenstorrent, and an HPCwire Person to Watch in 2021

April 22, 2021

As part of our HPCwire Person to Watch series, we are happy to present our interview with Jim Keller, president and chief technology officer of Tenstorrent. One of the top chip architects of our time, Keller has had an impactful career. Read more…

Senate Debate on Bill to Remake NSF – the Endless Frontier Act – Begins

May 18, 2021

The U.S. Senate today opened floor debate on the Endless Frontier Act which seeks to remake and expand the National Science Foundation by creating a technology Read more…

  • arrow
  • Click Here for More Headlines
  • arrow
HPCwire