Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT-ORNL governor's chair unlocks secrets of protein folding

18.09.2007
A team led by biophysicist Jeremy Smith of the University of Tennessee and Oak Ridge National Laboratory (ORNL) has taken a significant step toward unraveling the mystery of how proteins fold into unique, three-dimensional shapes.

Using ORNL's Cray XT4 Jaguar supercomputer as well as computer systems in Italy and Germany, the team revealed a driving force behind protein folding involving the way its constituents interact with water. The team's results are being published in this week's edition of the Proceedings of the National Academy of Sciences.

Proteins are the workhorses of the body, taking on a wide variety of tasks. They fight infections, turn food into energy, copy DNA and catalyze chemical reactions. Insulin is a protein, as are antibodies and many hormones.

Scientists are still very interested in deciphering how proteins work.

... more about:
»Molecule »Peptide »amino »determined »folding »hydrophobic

A protein is a string of amino acids, and what it does is determined by the shape it takes. That shape is determined by the sequence of the amino acids. Like a piece of biological origami, the protein folds itself into the form necessary to carry out its job. Without the shape the protein would be worthless.

"Understanding the mechanism by which proteins fold up into unique three-dimensional architectures is a holy grail in molecular biology," explained Smith, who holds the first UT-ORNL Governor's Chair and is a member of the Biochemistry and Molecular Biology Department at UT.

"Unfortunately, if you give me the sequence of amino acid building blocks in the protein, I cannot tell you what the structure would be," he said. "If I had been able to do that with a computer a while ago, the work behind about a dozen Nobel prizes -- those awarded for experimental work on protein structure determination -- would not have been necessary."

Working on a smaller chain of amino acids known as a peptide, the group showed that the folding is determined largely by how parts of the peptide interact with water. Areas that shun water are said to be hydrophobic, and the team's results show that the way water wets these hydrophobic areas determines the ultimate shape and behavior of the peptide.

In particular, the team determined that small hydrophobic areas of the peptide, up to the size of a water molecule, induce different behavior in water than larger hydrophobic areas, and that this difference is crucial for the folding. This insight builds on the work of another team, based at the University of California–Berkeley.

"David Chandler and his colleagues at Berkeley have a theory stating that hydrophobicity is qualitatively different on different length scales," Smith said. "If you have small hydrophobic molecules or groups that are themselves roughly the size of a water molecule, the water doesn't seem to be too bothered by these groups. But when you get hydrophobic entities as long as several water molecules, the water molecules have a problem with that. They can't cloak themselves around the hydrophobic surface anymore, and there is a dewetting or drying effect as they are repelled from the surface.

"Our simulations have shown that Chandler's theory works for peptides, and, moreover, that the drying effect determines which structure our peptide adopts. It's kind of 'dry it off then fold it up.'"

Smith said his team's achievement was made possible by high-performance computing, noting that Jaguar is currently rated the second most powerful computing system in the world. Smith also said that his team will need increasingly powerful supercomputers for additional simulation. While the team so far has been able to simulate about a microsecond in the life of a peptide, they must eventually be able to increase that time a thousand-fold, to milliseconds, and simulate proteins that are 10 to 100 times as large as the peptides.

"The runs were a couple of microseconds, which was adequate for the peptide that was simulated," Smith explained. "But the team is looking forward to increased computing capacity as it moves forward. The technique used is molecular dynamics simulation, and it needs high-performance leadership supercomputing to reach the length and timescales needed to fold a complete functional protein in the computer. With the projected capability improvements in Jaguar over the next couple of years, we will soon be approaching that goal."

Smith made it clear that the achievement would represent a watershed in the field.

"When we do eventually find out how to calculate protein structure from sequence," he said, "then a major revolution will come upon us, as we will have the basis to move forward with understanding much of biology and medicine, and the applications will range from rationally designing drugs to fit clefts in protein structures to engineering protein shapes for useful functions in nanotechnology and bioenergy."

Jay Mayfield | EurekAlert!
Further information:
http://www.tennessee.edu

Further reports about: Molecule Peptide amino determined folding hydrophobic

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>