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Primeur weekly 2016-11-21

Exascale supercomputing

Brookhaven Lab to lead and partner on DOE exascale computing projects ...

Quantum computing

World's fastest quantum simulator operating at the atomic level ...

Tracking the flow of quantum information ...

Tyndall technology lights the way for quantum computing ...

New attacks on location-based quantum cryptography ...

Focus on Europe

Fall 2016 edition of the e-IRG newsletter available ...

Fujitsu in joint intercontinental data centre coordination field trial using cold data storage ...

Asetek announces first installation using InRackCDU technology ...

Middleware

Altair PBS Cloud is Altair's latest technology to further HPC appliance solutions ...

Intel HPC Orchestrator to include PBS Pro for workload management ...

Altair expands the availability of PBS Professional ...

Adaptive Computing launches new Reporting & Analytics solution ...

Adaptive Computing opens up platform of products ...

Adaptive Computing improves ease-of-use & cost efficiency in Moab HPC Suite 9.1 release ...

Hardware

PGI accelerator compilers for POWER architecture enable easy on-ramp to GPU acceleration with POWER8 and NIVIDA NVLink ...

Liquid silicon: Computer chips could bridge the gap between computation and storage ...

Cray expands customer base for Cray Urika-GX system and previews upcoming software release ...

Fujitsu develops analysis technology to improve communication performance of virtual networks ...

Applications

NVIDIA teams with National Cancer Institute, U.S. Department of Energy to create AI platform for accelerating cancer research ...

Supercomputer simulations help develop new approach to fight antibiotic resistance ...

Earlham Institute receives supercomputing award for wheat research ...

Chinese research team that employs high performance computing to understand weather patterns wins 2016 ACM Gordon Bell Prize ...

Cray systems power deep learning in supercomputing at scale ...

IBM and Topcoder bring Watson to more than one million developers ...

IBM Watson Health and Broad Institute launch major research initiative to study why cancers become drug resistant ...

Julia for Astronomy: Parallel computing with Julia on NERSC supercomputer increases speed of image analysis 225x ...

Julia Computing and IBM present Julia for Deep Learning at SC16 ...

TOP500

Jefferson Lab's newest cluster makes TOP500 list of fastest supercomputers ...

Hewlett Packard Enterprise/SGI Cheyenne and Pleiades systems named on TOP500 list ...

The Cloud

Fujitsu and SUSE expand strategic alliance to develop and support open source products ...

IBM closes acquisition of Sanovi Technologies ...

Tencent Cloud joins IBM and Mellanox to break data sorting world records ...

Supercomputer simulations help develop new approach to fight antibiotic resistance


ORNL researchers used supercomputing to identify chemicals that seek out and disrupt the assembly of bacterial proteins called efflux pumps, known to be a major cause of antibiotic resistance. Credit: ORNL/University of Oklahoma.
17 Nov 2016 Oak Ridge - Supercomputer simulations at the Department of Energy's Oak Ridge National Laboratory have played a key role in discovering a new class of drug candidates that hold promise to combat antibiotic resistance. In a study led by the University of Oklahoma with ORNL, the University of Tennessee and Saint Louis University, lab experiments were combined with supercomputer modelling to identify molecules that boost antibiotics' effect on disease-causing bacteria.

The researchers found four new chemicals that seek out and disrupt bacterial proteins called "efflux pumps", known to be a major cause of antibiotic resistance. Although some antibiotics can permeate the protective barriers surrounding bacterial cells, many bacteria have evolved efflux pumps that expel antibiotics back out of the cell and render the medications ineffective.

The team focused on one efflux pump protein, known as AcrA, which connects two other proteins in a tunnel shape through the bacterial cell envelope. Disrupting this centrally positioned protein could "throw a wrench" into the middle of the efflux pump and mechanically break it, unlike drug design strategies that try to inhibit overall biochemical processes.

"As a first in this field, we proposed the approach of essentially 'screwing up' the efflux pump's protein assembly, and this led to the discovery of molecules with a new type of antibacterial activity", stated co-author Jeremy Smith, who serves as a UT-ORNL Governor's Chair and director of the UT-ORNL Center for Molecular Biophysics. "In contrast to previous approaches, our new mechanism uses mechanics to revive existing antibiotics' ability to fight infection." Details of the study were published inACS Infectious Diseases.

Through laboratory experiments done in tandem with extensive protein simulations run on ORNL's Titan supercomputer, they scanned large numbers of chemicals to predict and select which would be the most effective in preventing AcrA proteins from assembling properly.

"The supercomputing power of Titan allowed us to perform large-scale simulations of the drug targets and to screen many potential compounds quickly", stated Helen Zgurskaya, head of OU's Antibiotic Discovery and Resistance Group, who led the study. "The information we received was combined with our experiments to select molecules that were found to work well, and this should drastically reduce the time needed to move from the experimental phase to clinical trials."

Using computational models, researchers screened various combinations of molecules and proteins to determine which ones "fit" well together, similar to finding the right key for a specific lock. This process was complicated by the protein's dynamic nature; proteins constantly change their shape. In a simulated environment, researchers created virtual representations of the proteins, generated a series of protein "snapshots" in their various configurations and used Titan to "dock" thousands of molecules to each snapshot and estimate how strongly each would interact with the protein.

"The first screening took only 20 minutes using 42,000 processors and yielded several promising results", ORNL's Jerry Parks stated. "After more extensive analysis, we narrowed down our list to predict which molecules were most likely to disrupt the function of the efflux pump."

The research team members at the University of Oklahoma then conducted laboratory experiments to confirm the disruption of the efflux pump and the antibiotic-reviving capability for four of the molecules selected. Saint Louis University researchers then synthesized structural analogs of the discovered efflux pump inhibitors and identified properties essential for their activities.

The team's study focused on a prototypical type of efflux pump found inEscherichia colibacteria, but the researchers anticipate that their antibiotic-reviving approach will be applicable to many Gram-negative bacteria. They plan to leverage a recently awarded Innovative and Novel Computational Impact on Theory and Experiment (INCITE) allocation from DOE to perform larger simulations on the Titan supercomputer to gain deeper understanding of how bacterial efflux pumps function, identify more potent efflux pump inhibitors and optimize the best antibiotic-plus-inhibitor combinations to make them suitable for clinical trials.

The study titled, " Reviving Antibiotics: Efflux Pump Inhibitors That Interact with AcrA, a Membrane Fusion Protein of the AcrAB-TolC Multidrug Efflux Pump ", was led by OU's Helen Zgurskaya and co-authored by UT-ORNL's Jeremy Smith, Jerry Parks and Jerome Baudry; UT's Adam Green; Oklahoma Univeristy's Narges Abdali, Julie Chaney, David Wolloscheck and Valentin Rybenkov; and Saint Louis University's Keith Haynes and John Walker. The research was supported by a National Institutes of Health grant.
Source: DOE/Oak Ridge National Laboratory

Back to Table of contents

Primeur weekly 2016-11-21

Exascale supercomputing

Brookhaven Lab to lead and partner on DOE exascale computing projects ...

Quantum computing

World's fastest quantum simulator operating at the atomic level ...

Tracking the flow of quantum information ...

Tyndall technology lights the way for quantum computing ...

New attacks on location-based quantum cryptography ...

Focus on Europe

Fall 2016 edition of the e-IRG newsletter available ...

Fujitsu in joint intercontinental data centre coordination field trial using cold data storage ...

Asetek announces first installation using InRackCDU technology ...

Middleware

Altair PBS Cloud is Altair's latest technology to further HPC appliance solutions ...

Intel HPC Orchestrator to include PBS Pro for workload management ...

Altair expands the availability of PBS Professional ...

Adaptive Computing launches new Reporting & Analytics solution ...

Adaptive Computing opens up platform of products ...

Adaptive Computing improves ease-of-use & cost efficiency in Moab HPC Suite 9.1 release ...

Hardware

PGI accelerator compilers for POWER architecture enable easy on-ramp to GPU acceleration with POWER8 and NIVIDA NVLink ...

Liquid silicon: Computer chips could bridge the gap between computation and storage ...

Cray expands customer base for Cray Urika-GX system and previews upcoming software release ...

Fujitsu develops analysis technology to improve communication performance of virtual networks ...

Applications

NVIDIA teams with National Cancer Institute, U.S. Department of Energy to create AI platform for accelerating cancer research ...

Supercomputer simulations help develop new approach to fight antibiotic resistance ...

Earlham Institute receives supercomputing award for wheat research ...

Chinese research team that employs high performance computing to understand weather patterns wins 2016 ACM Gordon Bell Prize ...

Cray systems power deep learning in supercomputing at scale ...

IBM and Topcoder bring Watson to more than one million developers ...

IBM Watson Health and Broad Institute launch major research initiative to study why cancers become drug resistant ...

Julia for Astronomy: Parallel computing with Julia on NERSC supercomputer increases speed of image analysis 225x ...

Julia Computing and IBM present Julia for Deep Learning at SC16 ...

TOP500

Jefferson Lab's newest cluster makes TOP500 list of fastest supercomputers ...

Hewlett Packard Enterprise/SGI Cheyenne and Pleiades systems named on TOP500 list ...

The Cloud

Fujitsu and SUSE expand strategic alliance to develop and support open source products ...

IBM closes acquisition of Sanovi Technologies ...

Tencent Cloud joins IBM and Mellanox to break data sorting world records ...