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Primeur weekly 2014-03-17

Exascale supercomputing

Addressing the Big Data challenge in radio astronomy ...

The Cloud

VMware launches VMware Horizon DaaS to enable simple and flexible delivery of desktops in the Cloud ...

Oracle showcases next-generation Cloud applications user experiences in Europe ...

EuroFlash

More secure communications thanks to quantum physics ...

Signal control with light frequencies ...

International research into controlled nuclear fusion (ITER project), gets more compute resources with expansion of the Helios supercomputer ...

The SKA takes off with GBP119 million contribution from the UK ...

USFlash

Big Data tackles tiny molecular machines ...

Cirrascale announces support for Intel Xeon processor E5-4600 v2 product family with VB2400 and RM2400 product lines ...

Technologies developed for providing flexible wide area networks with SDN, a global first ...

NEC wins SEA-ME-WE 5 Contract to strengthen ultra-broadband undersea connectivity between Singapore and France NEC will deploy the segment from Singapore to Sri Lanka and co-contractor Alcatel-Lucent the segments from Sri Lanka to France ...

NEC's latest SDN release increases scalability 10x with new Unified Network Coordinator (UNC) ...

VMware announces general availability of VMware Virtual SAN ...

Terascala releases latest version of groundbreaking high performance data movement solution ...

Supermicro announces Cluster-in-a-Box storage solution running Windows Storage Server 2012 R2 standard edition ...

Supermicro spotlights extreme density, ultra low power 6U 112-node microblade and advanced computing technologies ...

'Ultracold' molecules promising for quantum computing and simulation ...

Quantum physics secures new cryptography scheme ...

Mellanox Announces LinkX the most comprehensive product family of cables and transceivers for data Centre infrastructures ...

Industry leaders introduce OpenOptics multi-source agreement ...

Wipro partners with SGI for rapid growth in India ...

Big Data tackles tiny molecular machines


Faruck Morcos/Rice University
14 Mar 2014 Houston - Open, feed, cut. Such is the humdrum life of a motor molecule, the subject of new research at Rice University, that eats and excretes damaged proteins and turns them into harmless peptides for disposal. The why is obvious: Without these trash bins, the Escherichia coli bacteria they serve would die. And thanks to Rice, the how is becoming clearer.

Biophysicists at Rice used the miniscule machine - a protease called an FtsH-AAA hexameric peptidase - as a model to test calculations that combine genetic and structural data. Their goal is to solve one of the most compelling mysteries in biology: how proteins perform the regulatory mechanisms in cells upon which life depends.

The Rice team of biological physicist José Onuchic and postdoctoral researchers Biman Jana and Faruck Morcos published a new paper on the work for a special issue of the Royal Society of Chemistry journal,Physical Chemistry Chemical Physics.

The special issue edited by Rice biophysicist Peter Wolynes and Ruth Nussinov, a researcher at the National Cancer Institute in Frederick, Maryland, and a professor at the Sackler School of Medicine at Tel Aviv University, pulls together current thinking on how an explosion of data combined with ever more powerful computers is bringing about a second revolution in molecular biology.

The paper describes the José Onuchic group's first successful attempt to feed data through their computational technique to describe the complex activity of a large molecular machine formed by proteins. Ultimately, understanding these machines will help researchers design drugs to treat diseases like cancer, the focus of Rice's Center for Theoretical Biological Physics.

"Structural techniques like X-ray crystallography and nuclear magnetic resonance have worked quite well to help us understand how smaller proteins function", José Onuchic stated. X-rays only take snapshots of constantly moving proteins, he said, "but functional proteins, big protein complexes and molecular machines have multiple conformations."

"Computational models are also useful, but to understand the full dynamics of these large proteins, where a lot of the interesting biology takes place, we have to supplement them with more information", he stated.

That information comes from direct coupling analysis (DCA), a statistical tool developed by Faruck Morcos and José Onuchic with colleagues at the University of California, San Diego, and the Pierre and Marie Curie University. DCA looks at the genetic roots of proteins to see how amino acids - the "beads" in the unfolded protein strands - co-evolved to influence the way a protein folds. Each bead carries an intrinsic energy that contributes to the strand's distinct energy landscape, which dictates how it folds into its functional state.

Even after they fold, proteins are in perpetual motion, acting as catalysts for countless bodily functions. They can combine into larger molecular machines that grab other molecules, "walk" cargoes within a cell or cause muscles to contract.

One such biomachine is FtsH, a membrane-bound molecule in E. coli made of six protein copies that form two connected hexagonal rings. The molecule attracts and degrades misfolded proteins and other cellular detritus, pulling them in through one ring, which closes like the shutter of a camera and traps the proteins. They are cut apart as they exit through the other ring.

Through molecular simulations using structure-based models and the discovery via DCA of likely couplings in the genetic source of the proteins, the Rice team found evidence to support the hypothesis of a "paddling" mechanism in the molecule that Faruck Morcos described as a collapse of the two rings once trash found its way inside.

"First the ring pore closes to grab the protein; then the molecule flattens", he stated. "Then when the motor is flat, the rings open to release the peptides and the molecule expands again to restart the cycle."

Key to the success of DCA is the realization that amino acid mutations represent contacts that co-evolve for specific purposes. The contact maps created by DCA can reveal previously unknown details to model transitions between functional states, like the paddling in FtsH, José Onuchic said.

"We can look at the evolutionary tree of these proteins and see which pairs of amino acids changed together. We then assume these are contacts", he stated. "Through DCA, Faruck uses a lot of physics to understand when two amino acids can act directly or indirectly, and separate the two. Then we predict how coupled they are, and the higher the probability, the more evidence that these are real contacts."

DCA would do little without the flood of data available since the ability to scan entire genomes became possible, and even commonplace, in recent decades. Advances in the century-old art of crystallography are making better structure-based models available as well.

"Even if the mathematical framework was ready and we had crystallographic data for this motor protein in the 1990s, there weren't enough sequences available until the 2000s", Faruck Morcos stated. "Now we have all the pieces converging."

He said understanding essential motor proteins in bacteria will be important as researchers begin to apply DCA to advance human health. "For us, the most exciting part is that we're now able to tackle really big systems", Faruck Morcos stated.

The research was supported by the Center for Theoretical Biological Physics, the Welch Foundation, the National Science Foundation and the Cancer Prevention and Research Institute of Texas. José Onuchic is the Harry C. and Olga K. Wiess Chair of Physics and Professor of Physics and Astronomy. Peter Wolynes is the D.R. Bullard-Welch Foundation Professor of Science and a professor of chemistry.

You can read the abstract at http://pubs.rsc.org/en/content/articlelanding/2014/cp/c3cp55275f#!divAbstract
Source: Rice University

Back to Table of contents

Primeur weekly 2014-03-17

Exascale supercomputing

Addressing the Big Data challenge in radio astronomy ...

The Cloud

VMware launches VMware Horizon DaaS to enable simple and flexible delivery of desktops in the Cloud ...

Oracle showcases next-generation Cloud applications user experiences in Europe ...

EuroFlash

More secure communications thanks to quantum physics ...

Signal control with light frequencies ...

International research into controlled nuclear fusion (ITER project), gets more compute resources with expansion of the Helios supercomputer ...

The SKA takes off with GBP119 million contribution from the UK ...

USFlash

Big Data tackles tiny molecular machines ...

Cirrascale announces support for Intel Xeon processor E5-4600 v2 product family with VB2400 and RM2400 product lines ...

Technologies developed for providing flexible wide area networks with SDN, a global first ...

NEC wins SEA-ME-WE 5 Contract to strengthen ultra-broadband undersea connectivity between Singapore and France NEC will deploy the segment from Singapore to Sri Lanka and co-contractor Alcatel-Lucent the segments from Sri Lanka to France ...

NEC's latest SDN release increases scalability 10x with new Unified Network Coordinator (UNC) ...

VMware announces general availability of VMware Virtual SAN ...

Terascala releases latest version of groundbreaking high performance data movement solution ...

Supermicro announces Cluster-in-a-Box storage solution running Windows Storage Server 2012 R2 standard edition ...

Supermicro spotlights extreme density, ultra low power 6U 112-node microblade and advanced computing technologies ...

'Ultracold' molecules promising for quantum computing and simulation ...

Quantum physics secures new cryptography scheme ...

Mellanox Announces LinkX the most comprehensive product family of cables and transceivers for data Centre infrastructures ...

Industry leaders introduce OpenOptics multi-source agreement ...

Wipro partners with SGI for rapid growth in India ...