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Primeur weekly 2018-10-08

Special

Where did the first 500 million euro invested by the European Horizon 2020 programme go? ...

Focus

World's first ARM-based supercomputer Isambard is ready for science ...

Exascale supercomputing

New European project ESCAPE-2 on exascale computing for numerical weather prediction gets under way ...

Berkeley Lab, Oak Ridge, and NVIDIA team breaks exaop barrier with deep learning application ...

Coming soon to exascale computing: Software for chemistry of catalysis ...

Quantum computing

ORNL researchers advance quantum computing, science through six DOE awards ...

Berkeley Lab to build an advanced quantum computing testbed ...

Berkeley Lab to push quantum information frontiers with new programmes in computing, physics, materials, and chemistry ...

Berkeley Quantum to accelerate innovation in quantum information science ...

Quantum software company Zapata Computing adds Clark Golestani to Board ...

Defects promise quantum communication through standard optical fiber ...

Focus on Europe

Atos and the University of Reims launch ROMEO, one of the most powerful supercomputers in the world, under the sponsorship of Cedric Villani ...

Special Edition of Open e-IRG Workshop under the Austrian EU Presidency will focus on relationship between Open Science, FAIR data and EOSC ...

Goethe University to develop green supercomputer for science ...

Calling on HPC experts and enthusiasts to propose tutorials and workshops for ISC 2019 ...

ISC 2019 calls for research paper submission by December 12, 2018 ...

Middleware

USC ISI to pilot Cyberinfrastructure Center of Excellence for National Science Foundation ...

Hardware

Tintri co-founder Mark Gritter joins Tintri by DDN as CTO to lead analytics and server virtualization vision ...

DDN simplifies the AI data centre with NVIDIA ...

New research could lead to more energy-efficient computing ...

Applications

New simulation sheds light on spiraling supermassive black holes ...

DNA unzipped, turned around, and rezipped ...

Dark Energy Survey releases first year value-added data products ...

A quantum leap toward expanding the search for dark matter ...

HP-CONCORD paves the way for scalable machine learning in HPC ...

In disaster's wake, novel computing techniques support emergency responders ...

Transition metal dichalcogenides could increase computer speed, memory by a million times ...

A new brain-inspired architecture could improve how computers handle data and advance AI ...

Rochester Institute of Technology leads multi-university collaboration to simulate neutron star mergers ...

The Cloud

Oracle rolls out Autonomous NoSQL Database service ...

Quanta Cloud Technology showcases AI portfolio options at GTC Europe ...

ZeroStack delivers GPU-as-a-Service via NVIDIA hardware ...

DNA unzipped, turned around, and rezipped

DNA helicase switches itself from unwinding double-strand DNA to a predicted rezipping state.4 Oct 2018 Urbana-Champaign - Scientists have long known that double-stranded DNA can be unwound into single-stranded DNA by molecular motor proteins called helicases, just like pulling a zipper. But researchers at the University of Illinois have discovered that the same machinery, after changing its shape, can also put the unwound DNA back together into double-stranded DNA.

This switching between DNA rewinding and unwinding was first reported in 2015 by Illinois physics professor Y.R. Chemla. Chemla's work caught the attention of Wen Ma, a post-doctoral researcher in biological physics at Illinois, who, along with his advisor, Zaida Luthey-Schulten, advanced Y.R. Chemla's work in a paper recently published in Elife . Wen Ma, who completed his PhD training under the late Klaus Schulten, does computational modelling of the molecular machines that play vital roles in a cell.

The unwinding is kind of conventional wisdom, said Wen Ma. If you have something happen to the cell to cause it to mutate, such as exposure to UV light and chemicals, in response helicases will unwind the double strand into a single strand DNA, so other cell machinery may be able to come in and repair it. Obviously, he noted, sometimes you don't want every piece of double-stranded DNA to be unwound by helicases too quickly. "So there must be some control mechanism which adjusts the activity of the helicase", he stated.

Wen Ma and his colleagues were intrigued by the thought that the DNA helicase - the molecular motor that drives the unwinding - could switch to rezipping, and set out to model it computationally with hopes of learning what that control mechanism was. By running the Nanoscale Molecular Dynamics (NAMD) code on the Blue Waters supercomputer at Illinois' National Center for Supercomputing Applications, Wen Ma was able to create a simulation that included "hundreds of thousands of atoms" and study the helicase in further detail.

Y.R. Chemla's research team had combined two cutting-edge experimental techniques in their discovery of the unwinding-rezipping switching - simultaneous single molecule fluorescence resonance energy transfer (smFRET) and optical tweezers. smFRET is a fluorescence methodology to detect protein conformation. Optical tweezers, which apply highly focused laser light to trap microscopic objects, are used to detect helicase unwinding activity. They observed that the protein unwinds the DNA, but it doesn't go very far, until it goes back in a different conformation and rezips the DNA. But it was unclear what the molecular mechanism was that regulated this behaviour.

Following the footsteps of the smFRET and optical tweezers work, Wen Ma and his colleagues used Blue Waters to model every single atom of the protein according to basic physical principles. Through this simulation, the first to provide this atomistic-level look at what is happening in the helicase, Wen Ma and his colleagues learned the protein is really doing a kind of switching function between the two states, unwinding and rezipping, in the timescale of millisecond or longer. This long simulation time scale, according to Wen Ma, was only able to be captured by using novel enhanced sampling simulations.

"This work is important", he stated, "because it enables us to link the atomic protein structure with its function. With other methodologies, like crystallography, you get a static image, and you don't know what happens dynamically. But with this simulation we learned why and how the DNA repair enzyme UvrD changes its conformation from the unzipping to the rezipping state, and we learned that the helicase tilts itself and forms stable interactions with the opposite strand once switched to rezipping. The simulation results were validated by the good agreement between the simulated smFRET efficiency for our predicted structure and the experimentally measured smFRET efficiency."

Wen Ma emphasized that there is still much to learn about helicase function and DNA repair. The potential for applying that knowledge is huge, as the information can aid those working on targeted drug design. Perhaps one day researchers will be able to use the revealed mechanism to help restore genome stability in related cancer cells.

The work of Wen Ma and his colleagues has been supported by the National Science Foundation's Center for the Physics of Living Cells and the National Institutes of Health.
Source: National Center for Supercomputing Applications - NCSA

Back to Table of contents

Primeur weekly 2018-10-08

Special

Where did the first 500 million euro invested by the European Horizon 2020 programme go? ...

Focus

World's first ARM-based supercomputer Isambard is ready for science ...

Exascale supercomputing

New European project ESCAPE-2 on exascale computing for numerical weather prediction gets under way ...

Berkeley Lab, Oak Ridge, and NVIDIA team breaks exaop barrier with deep learning application ...

Coming soon to exascale computing: Software for chemistry of catalysis ...

Quantum computing

ORNL researchers advance quantum computing, science through six DOE awards ...

Berkeley Lab to build an advanced quantum computing testbed ...

Berkeley Lab to push quantum information frontiers with new programmes in computing, physics, materials, and chemistry ...

Berkeley Quantum to accelerate innovation in quantum information science ...

Quantum software company Zapata Computing adds Clark Golestani to Board ...

Defects promise quantum communication through standard optical fiber ...

Focus on Europe

Atos and the University of Reims launch ROMEO, one of the most powerful supercomputers in the world, under the sponsorship of Cedric Villani ...

Special Edition of Open e-IRG Workshop under the Austrian EU Presidency will focus on relationship between Open Science, FAIR data and EOSC ...

Goethe University to develop green supercomputer for science ...

Calling on HPC experts and enthusiasts to propose tutorials and workshops for ISC 2019 ...

ISC 2019 calls for research paper submission by December 12, 2018 ...

Middleware

USC ISI to pilot Cyberinfrastructure Center of Excellence for National Science Foundation ...

Hardware

Tintri co-founder Mark Gritter joins Tintri by DDN as CTO to lead analytics and server virtualization vision ...

DDN simplifies the AI data centre with NVIDIA ...

New research could lead to more energy-efficient computing ...

Applications

New simulation sheds light on spiraling supermassive black holes ...

DNA unzipped, turned around, and rezipped ...

Dark Energy Survey releases first year value-added data products ...

A quantum leap toward expanding the search for dark matter ...

HP-CONCORD paves the way for scalable machine learning in HPC ...

In disaster's wake, novel computing techniques support emergency responders ...

Transition metal dichalcogenides could increase computer speed, memory by a million times ...

A new brain-inspired architecture could improve how computers handle data and advance AI ...

Rochester Institute of Technology leads multi-university collaboration to simulate neutron star mergers ...

The Cloud

Oracle rolls out Autonomous NoSQL Database service ...

Quanta Cloud Technology showcases AI portfolio options at GTC Europe ...

ZeroStack delivers GPU-as-a-Service via NVIDIA hardware ...