Drug Developers Use Google Cloud HPC in the Fight Against ALS

By Doug Black

February 16, 2017

Within the haystack of a lethal disease such as ALS (amyotrophic lateral sclerosis / Lou Gehrig’s Disease) there exists, somewhere, the needle that will pierce this therapy-resistant affliction. Finding the needle is a trial-and-error process of monumental proportions for scientists at pharmaceutical companies, medical research centers and academic institutions. As models grow in scale so too does the need for HPC resources to run simulations iteratively, to try-and-fail fast until success is found.

That’s all well and good if there’s ready access to HPC on premises. If not, drug developers, such as ALS researcher Dr. May Khanna, Pharmacology Department assistant professor at the University of Arizona, have turned to HPC resources provided by public cloud services. But using AWS, Azure or Google introduces a host of daunting compute management problems that tax the skills and time availability of most on-site IT staffs.

These tasks include data placement, instance provisioning, job scheduling, configuring software and networks, cluster startup and tear-down, cloud provider setup, cost management and instance health checking. To handle these cloud orchestration functions tied to 5,000 cores of Google Cloud Preemptive VMs (PVMs), Dr. Khanna and her team at Arizona turned to Cycle Computing to run “molecular docking” simulations at scale by Schrödinger Glide molecular modeling drug design software.

The results: simulations that would otherwise take months have been compressed to a few hours, short enough to be run during one of Dr. Khanna’s seminars and the output shared with students.

Dr. May Khanna

Developing new drugs to target a specific disease often starts with the building blocks of the compounds that become the drugs. The process begins with finding small molecules that can target specific proteins that, when combined, can interact in a way that becomes the disease’s starting point. The goal is to find a molecule that breaks the proteins apart. This is done by simulating how the small molecules dock to the specific protein locations. These simulations are computationally intensive, and many molecules need to be simulated to find a few good candidates.

Without powerful compute resources, researchers must artificially constrain their searches, limiting the number of molecules to simulate. And they only check an area of the protein known to be biologically active. Even with these constraints, running simulations takes a long time. Done right, molecular docking is an iterative process that requires simulation, biological verification, and then further refinement. Shortening the iteration time is important to advancing the research.

The objective of Dr. Khanna’s work was to simulate the docking of 1 million compounds to one target protein. After a simulation was complete, the protein was produced in the lab, and compounds were then tested with nuclear magnetic resonance spectroscopy.

“It’s a target (protein) that’s been implicated in ALS,” the energetic Dr. Khanna told EnterpriseTech (HPCwire‘s sister pub). “The idea is that the particular protein was very interesting, people who modulated it in different ways found some significant improvement in the ALS models they have with (lab) mice. The closer we can link biology to what we’re seeing as a target, the better chance of actually getting to a real therapeutic.”

“Modulating,” Dr. Khanna explained, is disrupting two proteins interacting in a way that is associated with ALS, a disease that currently afflicts about 20,000 Americans and for which there is no cure. “We’re trying to disrupt them, to release them to do their normal jobs,” she said.

She said CycleCloud plays a central role in running Schrödinger Glide simulations. Without Google Cloud PVMs, simulations would take too long and model sizes would be too small to generate meaningful results. Without CycleCloud, the management of 5,000 PVM nodes would not be possible.

CycleCloud provides a web-based GUI, a command line interface and APIs to define cloud-based clusters. It auto-scales clusters by instance types, maximum cluster size and costing parameters, deploying systems of up to 156,000 cores while validating each piece of the infrastructure. Additionally, it syncs in-house data repositories with cloud locations in a policy / job driven fashion, to lower costs.

It should be noted that the use of Google Cloud’s PVMs, while helping to hold down the cost of running simulations to $200, contribute an additional degree of complexity to Dr. Khanna’s project work. Preemptible compute capacity offers the advantage of a consistent price not subject to dynamic demand pricing, as are other public cloud instances. PVMs are assigned to a job for a finite period of time but – here’s the rub – they can be revoked at any moment. While Dr. Khanna’s workflow was ideal for leveraging PVMs, since it consists of small, short-running jobs, PVMs can disappear at without warning.

In the case of Dr. Khanna’s ALS research work, said Jason Stowe, CEO of Cycle Computing said, “if you’re willing to getting rid of the node, but you’re able to use it during that timeframe at substantially lower cost, that allows you get a lot more computing bang for your buck. CycleCloud automates the process, taking care of nodes that go away, making sure the environment isn’t corrupted, and other technical aspects that we take care of so the user doesn’t have to.”

The simulation process is divided into two parts. The first step uses the Schrödinger LigPrep package, which converts 2D structures to the 3D format used in the next stage. This stage started with 4 GB of input data staged to an NFS filer. The output data was approximately 800KB and was stored on the NFS filer as well. To get the simulation done as efficiently as possible, the workload was split into 300 smaller jobs to assist in scaling the next stage of the workflow. In total, the first stage consumed 1500 core-hours of computation.

The Schrödinger Glide software package performs the second stage of the process, where the actual docking simulation is performed. Each of the 300 sub-jobs consists of four stages, each with an attendant prep stage. The total consumption was approximately 20,000 core-hours using 5,000 cores of n1-highcpu-16 instances. Each instance had 16 virtual cores with 60 gigabytes of RAM. The CycleCloud software dynamically sized the cluster based on the number of jobs in queue and replaced preempted instances.

Dr. Khanna’s research is the early stages of a process that, if successful, could take several years before reaching human clinical trials.

“The faster we can do this, the less time we have to wait for results, so we can go back and test it again and try to figure out what compounds are really binding,” she said, “the faster the process can move along.”

Dr. Khanna said plans are in place to increase the size of the pool of potential compounds, as well as include other proteins in the simulation to look for interactions that would not typically be seen until later in the process. The team will also simulate over the entire surface of the protein instead of just a known-active area unlocking “an amazing amount of power” in the search process, she said.

“That jump between docking to binding to biological testing takes a really long time, but I think we can move forward on that with this cloud computing capacity,” she said. “The mice data that we saw was really exciting…, you could see true significant changes with the mice. I can’t tell you we’ve discovered the greatest thing for ALS, but showing that if we take these small molecules and we can see improvement, even that is so significant.”

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!

ASC18: Final Results Revealed & Wrapped Up

May 17, 2018

It was an exciting week at ASC18 in Nanyang, China. The student teams braved extreme heat, extremely difficult applications, and extreme competition in order to cross the cluster competition finish line. The gala awards ceremony took place on Wednesday. The auditorium was packed with student teams, various dignitaries, the media, and other interested parties. So what happened? Read more…

By Dan Olds

ASC18: Tough Applications & Tough Luck

May 17, 2018

The applications at the ASC18 Student Cluster Competition were tough. Tougher than the $3.99 steak special at your local greasy spoon restaurant. The apps are so tough that even Chuck Norris backs away from them slowly. Read more…

By Dan Olds

Spring Meetings Underscore Quantum Computing’s Rise

May 17, 2018

The month of April 2018 saw four very important and interesting meetings to discuss the state of quantum computing technologies, their potential impacts, and the technology challenges ahead. These discussions happened in Read more…

By Alex R. Larzelere

HPE Extreme Performance Solutions

HPC and AI Convergence is Accelerating New Levels of Intelligence

Data analytics is the most valuable tool in the digital marketplace – so much so that organizations are employing high performance computing (HPC) capabilities to rapidly collect, share, and analyze endless streams of data. Read more…

IBM Accelerated Insights

Mastering the Big Data Challenge in Cognitive Healthcare

Patrick Chain, genomics researcher at Los Alamos National Laboratory, posed a question in a recent blog: What if a nurse could swipe a patient’s saliva and run a quick genetic test to determine if the patient’s sore throat was caused by a cold virus or a bacterial infection? Read more…

Quantum Network Hub Opens in Japan

May 17, 2018

Following on the launch of its Q Commercial quantum network last December with 12 industrial and academic partners, the official Japanese hub at Keio University is now open to facilitate the exploration of quantum applications important to science and business. The news comes a week after IBM announced that North Carolina State University was the first U.S. university to join its Q Network. Read more…

By Tiffany Trader

ASC18: Final Results Revealed & Wrapped Up

May 17, 2018

It was an exciting week at ASC18 in Nanyang, China. The student teams braved extreme heat, extremely difficult applications, and extreme competition in order to cross the cluster competition finish line. The gala awards ceremony took place on Wednesday. The auditorium was packed with student teams, various dignitaries, the media, and other interested parties. So what happened? Read more…

By Dan Olds

Spring Meetings Underscore Quantum Computing’s Rise

May 17, 2018

The month of April 2018 saw four very important and interesting meetings to discuss the state of quantum computing technologies, their potential impacts, and th Read more…

By Alex R. Larzelere

Quantum Network Hub Opens in Japan

May 17, 2018

Following on the launch of its Q Commercial quantum network last December with 12 industrial and academic partners, the official Japanese hub at Keio University is now open to facilitate the exploration of quantum applications important to science and business. The news comes a week after IBM announced that North Carolina State University was the first U.S. university to join its Q Network. Read more…

By Tiffany Trader

Democratizing HPC: OSC Releases Version 1.3 of OnDemand

May 16, 2018

Making HPC resources readily available and easier to use for scientists who may have less HPC expertise is an ongoing challenge. Open OnDemand is a project by t Read more…

By John Russell

PRACE 2017 Annual Report: Exascale Aspirations; Industry Collaboration; HPC Training

May 15, 2018

The Partnership for Advanced Computing in Europe (PRACE) today released its annual report showcasing 2017 activities and providing a glimpse into thinking about Read more…

By John Russell

US Forms AI Brain Trust

May 11, 2018

Amid calls for a U.S. strategy for promoting AI development, the Trump administration is forming a senior-level panel to help coordinate government and industry research efforts. The Select Committee on Artificial Intelligence was announced Thursday (May 10) during a White House summit organized by the Office of Science and Technology Policy (OSTP). Read more…

By George Leopold

Emerging Advanced Scale Tech Trends Focus of Annual Tabor Conference

May 9, 2018

At Tabor Communications' annual Advanced Scale Forum (ASF) held this week in Austin, the focus was on enterprise adoption of HPC-class technologies and high performance data analytics (HPDA). It’s a confab that brings together end users (CIOs, IT planners, department heads) and vendors and encourages... Read more…

By the Editorial Team

Google I/O 2018: AI Everywhere; TPU 3.0 Delivers 100+ Petaflops but Requires Liquid Cooling

May 9, 2018

All things AI dominated discussion at yesterday’s opening of Google’s I/O 2018 developers meeting covering much of Google's near-term product roadmap. The e Read more…

By John Russell

MLPerf – Will New Machine Learning Benchmark Help Propel AI Forward?

May 2, 2018

Let the AI benchmarking wars begin. Today, a diverse group from academia and industry – Google, Baidu, Intel, AMD, Harvard, and Stanford among them – releas Read more…

By John Russell

How the Cloud Is Falling Short for HPC

March 15, 2018

The last couple of years have seen cloud computing gradually build some legitimacy within the HPC world, but still the HPC industry lies far behind enterprise I Read more…

By Chris Downing

Russian Nuclear Engineers Caught Cryptomining on Lab Supercomputer

February 12, 2018

Nuclear scientists working at the All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) have been arrested for using lab supercomputing resources to mine crypto-currency, according to a report in Russia’s Interfax News Agency. Read more…

By Tiffany Trader

Inventor Claims to Have Solved Floating Point Error Problem

January 17, 2018

"The decades-old floating point error problem has been solved," proclaims a press release from inventor Alan Jorgensen. The computer scientist has filed for and Read more…

By Tiffany Trader

Researchers Measure Impact of ‘Meltdown’ and ‘Spectre’ Patches on HPC Workloads

January 17, 2018

Computer scientists from the Center for Computational Research, State University of New York (SUNY), University at Buffalo have examined the effect of Meltdown 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

Deep Learning at 15 PFlops Enables Training for Extreme Weather Identification at Scale

March 19, 2018

Petaflop per second deep learning training performance on the NERSC (National Energy Research Scientific Computing Center) Cori supercomputer has given climate Read more…

By Rob Farber

AI Cloud Competition Heats Up: Google’s TPUs, Amazon Building AI Chip

February 12, 2018

Competition in the white hot AI (and public cloud) market pits Google against Amazon this week, with Google offering AI hardware on its cloud platform intended Read more…

By Doug Black

Leading Solution Providers

US Plans $1.8 Billion Spend on DOE Exascale Supercomputing

April 11, 2018

On Monday, the United States Department of Energy announced its intention to procure up to three exascale supercomputers at a cost of up to $1.8 billion with th Read more…

By Tiffany Trader

Lenovo Unveils Warm Water Cooled ThinkSystem SD650 in Rampup to LRZ Install

February 22, 2018

This week Lenovo took the wraps off the ThinkSystem SD650 high-density server with third-generation direct water cooling technology developed in tandem with par Read more…

By Tiffany Trader

HPC and AI – Two Communities Same Future

January 25, 2018

According to Al Gara (Intel Fellow, Data Center Group), high performance computing and artificial intelligence will increasingly intertwine as we transition to Read more…

By Rob Farber

Google Chases Quantum Supremacy with 72-Qubit Processor

March 7, 2018

Google pulled ahead of the pack this week in the race toward "quantum supremacy," with the introduction of a new 72-qubit quantum processor called Bristlecone. Read more…

By Tiffany Trader

HPE Wins $57 Million DoD Supercomputing Contract

February 20, 2018

Hewlett Packard Enterprise (HPE) today revealed details of its massive $57 million HPC contract with the U.S. Department of Defense (DoD). The deal calls for HP Read more…

By Tiffany Trader

CFO Steps down in Executive Shuffle at Supermicro

January 31, 2018

Supermicro yesterday announced senior management shuffling including prominent departures, the completion of an audit linked to its delayed Nasdaq filings, and Read more…

By John Russell

Deep Learning Portends ‘Sea Change’ for Oil and Gas Sector

February 1, 2018

The billowing compute and data demands that spurred the oil and gas industry to be the largest commercial users of high-performance computing are now propelling Read more…

By Tiffany Trader

Nvidia Ups Hardware Game with 16-GPU DGX-2 Server and 18-Port NVSwitch

March 27, 2018

Nvidia unveiled a raft of new products from its annual technology conference in San Jose today, and despite not offering up a new chip architecture, there were still a few surprises in store for HPC hardware aficionados. Read more…

By Tiffany Trader

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