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Primeur weekly 2017-04-10

Exascale supercomputing

EUROSERVER paves the way for low-power data centres ...

Intersect360 Research to provide USCC testimony for China's Pursuit of Next Frontier Tech hearing ...

Quantum computing

'Virtual' interferometers may overcome scale issues for optical quantum computers ...

Quantum-physical model system ...

Optics advance quantum information processing ...

Focus on Europe

A glance into the ISC 2017 Research Paper Session ...

OCF announce Iceotope as liquid cooling partner for research and academic market ...

Return of the mini-supercomputer in the Netherlands: Little Green Machine II ...

Max Planck Institute for Biophysical Chemistry chooses vSMP Foundation ...

PRACE opens SHAPE 5th Call for Proposals ...

IBM invests to accelerate innovation, collaboration and fast-track health care solutions in Finland ...

73% of academics say access to research data helps them in their work; 34% do not publish their data ...

Middleware

DDN Lustre powers University of Edinburgh accelerated genomics research ...

Hardware

Supercomputer growth drives record HPC revenue in 2016, Hyperion Research reports ...

Canada's most powerful academic supercomputer will launch at Simon Fraser University ...

Silicon Mechanics Announces Recipient of 6th Annual Research Cluster Grant ...

U.S. businesses risk falling behind as lead in global semiconductor industry threatened ...

Fujitsu and Oracle launch Fujitsu SPARC M12 servers with world's fastest per-core performance ...

IBM Researchers advance the understanding of chip reliability at IEEE International Reliability Physics Symposium ...

Applications

Artificial intelligence: Bosch and University of Amsterdam to cooperate closely ...

Cyber gene network could speed up discoveries ...

How can network analysis lead to a new way of studying court decisions? ...

IBM patents machine learning models for drug discovery ...

Clemson scientists receive $2.95 million to improve and simplify large-scale data analysis ...

New brain-inspired cybersecurity system detects 'bad apples' 100 times faster ...

Supercomputers reveal how cell membranes keep cancer-causing proteins turned off ...

The Cloud

IBM opens Budapest Software Lab to develop Cloud Video solutions ...

IBM first to deliver latest NVIDIA GPU accelerator on the Cloud to speed AI workloads ...

University of Wyoming uses Oracle Cloud to drive core mission of teaching, research, and service ...

Industry experts discuss advantages and risks of shifting data analytics to the Cloud ...

Supercomputers reveal how cell membranes keep cancer-causing proteins turned off


Credit: Cell Structure DOI: http://dx.doi.org/10.1016/j.str.2017.02.007.
4 Apr 2017 - Two biophysicists from Case Western Reserve University School of Medicine have used supercomputers to show how cell membranes control the shape, and consequently the function, of a major cancer-causing protein.

In a series of simulations described in the journalStructure, researchers discovered how fats and electrical charges in cell membranes can completely change the orientation of K-Ras. Too much of one particular type of fat, or lipid, in a membrane shifts and turns K-Ras, shoving its active portion away from the membrane and into the cell, where it can transmit cancer-causing signals. Other membrane lipids help tuck portions of the cancer-driving protein away, putting it in close contact with the membrane and thereby rendering it inactive.

"Experimental studies have shown that the orientation of the cancer-causing K-Ras protein at the membrane matters for its function", stated Matthias Buck, PhD, study lead and professor of physiology and biophysics, Case Western Reserve University School of Medicine, and a member of the Case Comprehensive Cancer Center. "We found that a particular type of membrane lipid, PIP2, turns the protein to an orientation that allows it to become active and promote cancer."

The discovery suggests limiting concentrations of PIP2 in cell membranes could help keep the harmful K-Ras protein hidden by the membrane in the "off" position. "The finding that certain cell signaling lipids change the activity of an oncogenic Ras protein, suggests that we might be able to interfere with tumour progression by inhibiting the enzymes which make the specific cell signaling lipid in cells", Matthias Buck stated.

The study was inspired by Matthias Buck's co-author, Zhen-Lu (Andrew) Li, PhD, postdoctoral scholar in the department of physiology and biophysics at Case Western Reserve University School of Medicine. As Matthias Buck related: "He looked at the structure of the K-Ras protein and how it interacts with the membrane carefully. He found that the protein is not a 'round sphere' but rather a 'pyramid-like structure'. Thus, there are only five surfaces that can be used to interact with the membrane."

Armed with this revelation, the researchers studied all five K-Ras orientations in computer simulations that placed the protein at different membranes, mimicking physiological situations. Each simulation allowed the researchers to predict, down to the atom, how K-Ras would spin and orient itself in response to the membrane's composition, and the extent of electrical charges on each of its surfaces.

"We represent all atoms of our protein in a 'virtual space' in the computer. How atoms interact and exert forces on each other has been defined over many decades of work, allowing us to predict the motion of protein regions and also their structures", explained Matthias Buck. "In this way, modern supercomputers allow millions of small timesteps of atomic motions to be simulated, getting us to examine the protein but also cellular membrane behavior on the microsecond timescale."

Such real-time simulations require enormous computer power. "We have been lucky to get time on a specialized computer for molecular dynamics simulations, called Anton, at the Pittsburgh Supercomputer Center for the last several years. The Case High Performance Computing Cluster and the Ohio Supercomputer Center have also helped us to carry out the simulations, which often take several weeks, if not months of computer time", Matthias Buck stated.

K-Ras has long been a top target for drug design. But the new study reveals harmful physical characteristics of the protein may be due to its membrane environment. This insight could help drive new innovations in cancer prevention. Zhen-Lu Li summarized: "Features of K-Ras-membrane interactions may steer us in a different and novel direction for drug design. Instead of directly targeting K-Ras, the membrane may also be considered."

Funding for the study was provided by a grant from the National Institute of General Medical Science (R01GM112491 to M.B.). The Ohio Supercomputer Center in Columbus, Ohio provided computational resources, and Anton computer time was provided by the Pittsburgh Supercomputing Center through National Institutes of Health grant R01GM116961.
Source: Case Western Reserve University

Back to Table of contents

Primeur weekly 2017-04-10

Exascale supercomputing

EUROSERVER paves the way for low-power data centres ...

Intersect360 Research to provide USCC testimony for China's Pursuit of Next Frontier Tech hearing ...

Quantum computing

'Virtual' interferometers may overcome scale issues for optical quantum computers ...

Quantum-physical model system ...

Optics advance quantum information processing ...

Focus on Europe

A glance into the ISC 2017 Research Paper Session ...

OCF announce Iceotope as liquid cooling partner for research and academic market ...

Return of the mini-supercomputer in the Netherlands: Little Green Machine II ...

Max Planck Institute for Biophysical Chemistry chooses vSMP Foundation ...

PRACE opens SHAPE 5th Call for Proposals ...

IBM invests to accelerate innovation, collaboration and fast-track health care solutions in Finland ...

73% of academics say access to research data helps them in their work; 34% do not publish their data ...

Middleware

DDN Lustre powers University of Edinburgh accelerated genomics research ...

Hardware

Supercomputer growth drives record HPC revenue in 2016, Hyperion Research reports ...

Canada's most powerful academic supercomputer will launch at Simon Fraser University ...

Silicon Mechanics Announces Recipient of 6th Annual Research Cluster Grant ...

U.S. businesses risk falling behind as lead in global semiconductor industry threatened ...

Fujitsu and Oracle launch Fujitsu SPARC M12 servers with world's fastest per-core performance ...

IBM Researchers advance the understanding of chip reliability at IEEE International Reliability Physics Symposium ...

Applications

Artificial intelligence: Bosch and University of Amsterdam to cooperate closely ...

Cyber gene network could speed up discoveries ...

How can network analysis lead to a new way of studying court decisions? ...

IBM patents machine learning models for drug discovery ...

Clemson scientists receive $2.95 million to improve and simplify large-scale data analysis ...

New brain-inspired cybersecurity system detects 'bad apples' 100 times faster ...

Supercomputers reveal how cell membranes keep cancer-causing proteins turned off ...

The Cloud

IBM opens Budapest Software Lab to develop Cloud Video solutions ...

IBM first to deliver latest NVIDIA GPU accelerator on the Cloud to speed AI workloads ...

University of Wyoming uses Oracle Cloud to drive core mission of teaching, research, and service ...

Industry experts discuss advantages and risks of shifting data analytics to the Cloud ...