Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bold Move Forward in Molecular Analyses

26.04.2013
Berkeley Lab Researchers Develop New Metrics for X-ray and Neutron Analysis of Flexible Macromolecules

A dramatic leap forward in the ability of scientists to study the structural states of macromolecules such as proteins and nanoparticles in solution has been achieved by a pair of researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab).


Small angle scattering (SAS) with X-rays (pictured here) or neutrons is the only imaging technique that provides a complete snapshot of the thermodynamic state of macromolecules in a single image.

The researchers have developed a new set of metrics for analyzing data acquired via small angle scattering (SAS) experiments with X-rays (SAXS) or neutrons (SANS). Among other advantages, this will reduce the time required to collect data by up to 20 times.

“SAS is the only technique that provides a complete snapshot of the thermodynamic state of macromolecules in a single image,” says Robert Rambo, a scientist with Berkeley Lab’s Physical Biosciences Division, who developed the new SAS metrics along with John Tainer of Berkeley Lab’s Life Sciences Division and the Scripps Research Institute.

“In the past, SAS analyses have focused on particles that were well-behaved in the sense that they assume discrete structural states,” Rambo says. “But in biology, many proteins and protein complexes are not well-behaved, they can be highly flexible, creating diffuse structural states. Our new set of metrics fully extends SAS to all particle types, well-behaved and not well-behaved.”

Rambo and Tainer describe their new SAS metrics in a paper titled “Accurate assessment of mass, models and resolution by small-angle scattering.” The paper has been published in the journal Nature.

Says co-author Tainer, “The SAS metrics reported in our Nature paper should have game-changing impacts on accurate high-throughput and objective analyses of the flexible molecular machines that control cell biology.”

In SAS imaging, beams of X-rays or neutrons sent through a sample produce tiny collisions between the X-rays or neutrons and nano- or subnano-sized particles within the sample. How these collisions scatter are unique for each particle and can be measured to determine the particle’s shape and size. The analytic metrics developed by Rambo and Tainer are predicated on the discovery by Rambo of an SAS invariant, meaning its value does not change no matter how or where the measurement was performed. This invariant has been dubbed the “volume-of-correlation” and its value is derived from the scattered intensities of X-rays or neutrons that are specific to the structural states of particles, yet are independent of their concentrations and compositions.

“The volume-of-correlation can be used for following the shape changes of a protein or nanoparticle, or as a quality metric for seeing if the data collection was corrupted,” Rambo says. “This SAS invariant applies equally well to compact and flexible particles, and utilizes the entire dataset, which makes it more reliable than traditional SAS analytics, which utilize less than 10-percent of the data.”

The volume-of-correlation was shown to also define a ratio that determines the molecular mass of a particle. Accurate determination of molecular mass has been a major difficulty in SAS analysis because previous methods required an accurate particle concentration, the assumption of a compact near-spherical shape, or measurements on an absolute scale.

“Such requirements hinder both accuracy and throughput of mass estimates by SAS,” Rambo says. “We’ve established a SAS-based statistic suitable for determining the molecular mass of proteins, nucleic acids or mixed complexes in solution without concentration or shape assumptions.”

The combination of the volume-of-correlation with other metrics developed by Rambo and Tainer can provide error-free recovery of SAS data with a signal-to-noise ratio below background levels. This holds profound implications for high-throughput SAS data collection strategies not only for current synchrotron-based X-ray sources, such as Berkeley Lab’s Advanced Light Source, but also for the next-generation light sources based on free-electron lasers that are now being designed.

“With our metrics, it should be possible to collect and analyze SAS data at the theoretical limit,” Rambo says. “This means we can reduce data collection times so that a 90- minute exposure time used by commercial instruments could be cut to nine minutes.”

Adds Tainer, “The discovery of the first x-ray scattering invariant coincided with the genesis of the Berkeley Lab some 75 years ago. This new discovery of the volume-of-correlation invariant unlocks doors for future analyses of flexible biological samples on the envisioned powerful next-generation light sources.

This research was funded through DOE’s Office of Science and the National Institutes of Health.

Lawrence Berkeley National Laboratory addresses the world’s most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab’s scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy’s Office of Science. For more, visit www.lbl.gov.

DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit the Office of Science website at science.energy.gov/.

Lynn Yarris | EurekAlert!
Further information:
http://www.lbl.gov

More articles from Physics and Astronomy:

nachricht Engineering team images tiny quasicrystals as they form
18.08.2017 | Cornell University

nachricht Astrophysicists explain the mysterious behavior of cosmic rays
18.08.2017 | Moscow Institute of Physics and Technology

All articles from Physics and Astronomy >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>