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!

New CMU AI Poker Bot – Pluribus – Humbles the Pros Again

July 15, 2019

Remember Libratus, the Carnegie Mellon University developed AI poker bot that’s been humbling poker professionals at Texas hold’em for a couple of years. Well, say hello to Pluribus, an upgraded bot, which has now be Read more…

By John Russell

ISC19 Cluster Competition: Application Results, Finally!

July 15, 2019

Our exhaustive coverage of the ISC19 Student Cluster Competition continues as we discuss the application scores below. While the scores were typically high, some of the apps, like SWIFT and OpenFOAM, really pushed the st Read more…

By Dan Olds

Portugal Launches Its First Supercomputer

July 12, 2019

Portugal has officially inaugurated its first-ever supercomputer. The unassumingly named “Bob” supercomputer is housed in the Minho Advanced Computer Center (MACC) at the University of Minho.  Bob was announced i Read more…

By Oliver Peckham

HPE Extreme Performance Solutions

HPE and Intel® Omni-Path Architecture: How to Power a Cloud

Learn how HPE and Intel® Omni-Path Architecture provide critical infrastructure for leading Nordic HPC provider’s HPCFLOW cloud service.

For decades, HPE has been at the forefront of high-performance computing, and we’ve powered some of the fastest and most robust supercomputers in the world. Read more…

IBM Accelerated Insights

How AI Powers Up Data Management and Analytics

Companies are making more decisions based on data. However, the ability to intelligently process the growing volume of data is a bottleneck to extracting actionable insights. Read more…

What’s New in HPC Research: Traffic Simulation, Performance Variations, Scheduling & More

July 11, 2019

In this bimonthly feature, HPCwire highlights newly published research in the high-performance computing community and related domains. From parallel programming to exascale to quantum computing, the details are here. Read more…

By Oliver Peckham

New CMU AI Poker Bot – Pluribus – Humbles the Pros Again

July 15, 2019

Remember Libratus, the Carnegie Mellon University developed AI poker bot that’s been humbling poker professionals at Texas hold’em for a couple of years. We Read more…

By John Russell

ISC19 Cluster Competition: Application Results, Finally!

July 15, 2019

Our exhaustive coverage of the ISC19 Student Cluster Competition continues as we discuss the application scores below. While the scores were typically high, som Read more…

By Dan Olds

Nvidia Expands DGX-Ready AI Program to 19 Countries

July 11, 2019

Nvidia’s DGX-Ready Data Center Program, announced in January and designed to provide colo and public cloud-like options to access the company’s GPU-powered Read more…

By Doug Black

Argonne Team Makes Record Globus File Transfer

July 10, 2019

A team of scientists at Argonne National Laboratory has broken a data transfer record by moving a staggering 2.9 petabytes of data for a research project.  The data – from three large cosmological simulations – was generated and stored on the Summit supercomputer at the Oak Ridge Leadership Computing Facility (OLCF)... Read more…

By Oliver Peckham

Nvidia, Google Tie in Second MLPerf Training ‘At-Scale’ Round

July 10, 2019

Results for the second round of the AI benchmarking suite known as MLPerf were published today with Google Cloud and Nvidia each picking up three wins in the at Read more…

By Tiffany Trader

Applied Materials Embedding New Memory Technologies in Chips

July 9, 2019

Applied Materials, the $17 billion Santa Clara-based materials engineering company for the semiconductor industry, today announced manufacturing systems enablin Read more…

By Doug Black

ISC19 Cluster Competition: HPCC Deep Dive

July 7, 2019

The biggest benchmark the student warriors tackled during the ISC19 Student Cluster Competition was the colossal HPC Challenge. This is a collection of benchmar Read more…

By Dan Olds

OLCF Bids Farewell to Its Titan Supercomputer

July 4, 2019

After seven years of faithful service, and a long reign as the United States' fastest supercomputer, the Cray XK7-based Titan supercomputer at the Oak Ridge Lea Read more…

By Staff report

High Performance (Potato) Chips

May 5, 2006

In this article, we focus on how Procter & Gamble is using high performance computing to create some common, everyday supermarket products. Tom Lange, a 27-year veteran of the company, tells us how P&G models products, processes and production systems for the betterment of consumer package goods. Read more…

By Michael Feldman

Cray, AMD to Extend DOE’s Exascale Frontier

May 7, 2019

Cray and AMD are coming back to Oak Ridge National Laboratory to partner on the world’s largest and most expensive supercomputer. The Department of Energy’s Read more…

By Tiffany Trader

Graphene Surprises Again, This Time for Quantum Computing

May 8, 2019

Graphene is fascinating stuff with promise for use in a seeming endless number of applications. This month researchers from the University of Vienna and Institu Read more…

By John Russell

AMD Verifies Its Largest 7nm Chip Design in Ten Hours

June 5, 2019

AMD announced last week that its engineers had successfully executed the first physical verification of its largest 7nm chip design – in just ten hours. The AMD Radeon Instinct Vega20 – which boasts 13.2 billion transistors – was tested using a TSMC-certified Calibre nmDRC software platform from Mentor. Read more…

By Oliver Peckham

TSMC and Samsung Moving to 5nm; Whither Moore’s Law?

June 12, 2019

With reports that Taiwan Semiconductor Manufacturing Co. (TMSC) and Samsung are moving quickly to 5nm manufacturing, it’s a good time to again ponder whither goes the venerable Moore’s law. Shrinking feature size has of course been the primary hallmark of achieving Moore’s law... Read more…

By John Russell

It’s Official: Aurora on Track to Be First US Exascale Computer in 2021

March 18, 2019

The U.S. Department of Energy along with Intel and Cray confirmed today that an Intel/Cray supercomputer, "Aurora," capable of sustained performance of one exaf Read more…

By Tiffany Trader

Deep Learning Competitors Stalk Nvidia

May 14, 2019

There is no shortage of processing architectures emerging to accelerate deep learning workloads, with two more options emerging this week to challenge GPU leader Nvidia. First, Intel researchers claimed a new deep learning record for image classification on the ResNet-50 convolutional neural network. Separately, Israeli AI chip startup Hailo.ai... Read more…

By George Leopold

Nvidia Embraces Arm, Declares Intent to Accelerate All CPU Architectures

June 17, 2019

As the Top500 list was being announced at ISC in Frankfurt today with an upgraded petascale Arm supercomputer in the top third of the list, Nvidia announced its Read more…

By Tiffany Trader

Leading Solution Providers

ISC 2019 Virtual Booth Video Tour

CRAY
CRAY
DDN
DDN
DELL EMC
DELL EMC
GOOGLE
GOOGLE
ONE STOP SYSTEMS
ONE STOP SYSTEMS
PANASAS
PANASAS
VERNE GLOBAL
VERNE GLOBAL

Top500 Purely Petaflops; US Maintains Performance Lead

June 17, 2019

With the kick-off of the International Supercomputing Conference (ISC) in Frankfurt this morning, the 53rd Top500 list made its debut, and this one's for petafl Read more…

By Tiffany Trader

Intel Launches Cascade Lake Xeons with Up to 56 Cores

April 2, 2019

At Intel's Data-Centric Innovation Day in San Francisco (April 2), the company unveiled its second-generation Xeon Scalable (Cascade Lake) family and debuted it Read more…

By Tiffany Trader

Cray – and the Cray Brand – to Be Positioned at Tip of HPE’s HPC Spear

May 22, 2019

More so than with most acquisitions of this kind, HPE’s purchase of Cray for $1.3 billion, announced last week, seems to have elements of that overused, often Read more…

By Doug Black and Tiffany Trader

A Behind-the-Scenes Look at the Hardware That Powered the Black Hole Image

June 24, 2019

Two months ago, the first-ever image of a black hole took the internet by storm. A team of scientists took years to produce and verify the striking image – an Read more…

By Oliver Peckham

Why Nvidia Bought Mellanox: ‘Future Datacenters Will Be…Like High Performance Computers’

March 14, 2019

“Future datacenters of all kinds will be built like high performance computers,” said Nvidia CEO Jensen Huang during a phone briefing on Monday after Nvidia revealed scooping up the high performance networking company Mellanox for $6.9 billion. Read more…

By Tiffany Trader

Announcing four new HPC capabilities in Google Cloud Platform

April 15, 2019

When you’re running compute-bound or memory-bound applications for high performance computing or large, data-dependent machine learning training workloads on Read more…

By Wyatt Gorman, HPC Specialist, Google Cloud; Brad Calder, VP of Engineering, Google Cloud; Bart Sano, VP of Platforms, Google Cloud

Chinese Company Sugon Placed on US ‘Entity List’ After Strong Showing at International Supercomputing Conference

June 26, 2019

After more than a decade of advancing its supercomputing prowess, operating the world’s most powerful supercomputer from June 2013 to June 2018, China is keep Read more…

By Tiffany Trader

In Wake of Nvidia-Mellanox: Xilinx to Acquire Solarflare

April 25, 2019

With echoes of Nvidia’s recent acquisition of Mellanox, FPGA maker Xilinx has announced a definitive agreement to acquire Solarflare Communications, provider Read more…

By Doug Black

  • arrow
  • Click Here for More Headlines
  • arrow
Do NOT follow this link or you will be banned from the site!
Share This