Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Slicing proteins with Occam's Razor

Vermont scientists invent new way to view atomic motion of proteins

A cheetah lies still in the grass. Finally, a gazelle comes into view. The cheetah plunges forward, reaches sixty-five miles per hour in three seconds, and has the hapless gazelle by the jugular in less than a minute. Then it must catch its breath, resting before eating.

A blue whale surfaces, blasting water high from its blowhole. It breathes in great gasps, filling its thousand-gallon lungs with air. Then it descends again to look for krill, staying below for 10, 20, even 30 minutes before taking another breath.

Both animals need oxygen, of course. And both depend on the protein myoglobin to store and then release that oxygen within their working muscles. But how they need oxygen differs. The whale must have enough to last a whole dive. Its muscles have a high concentration of myoglobin that delivers oxygen steadily. In contrast, the cheetah's myoglobin must perform like a fast-shooting cannon. The cheetah needs to suddenly take up and release large doses of oxygen to stoke its explosive speed.

How does myoglobin do all that? For decades, biologists have wondered how -- and with what atomic motions, exactly -- the folded structure of myoglobin allows it to hold and release oxygen.

Now, two physicists at the University of Vermont have an answer. They've developed a new way to peer into the inner workings of proteins and detect which specific atoms are at work. Their work was published in the Aug. 27 issue of the journal Physical Review Letters.

Using myoglobin as a test, the scientists were able to home in on the critical functional piece of the protein, separating it from the vast number of other "jigglings and wigglings of atoms" says William DeWitt, a UVM graduate student and the lead author on the paper that describes the finding.

"We've been able to identify the motion of one particular amino acid -- this group of atoms called the distal histidine -- that controls the binding process," he says.

Shaped a bit like a tennis racket over a basket, this tiny arm of the protein moves, through thermal fluctuations, to open or close the binding site near the myoglobin's iron-filled center. "As the atoms move in one direction it becomes easier to bind oxygen," says DeWitt, "and as they move in the reverse direction it becomes less easy."

And how this distal histidine moves should vary between the whale and the cheetah. "I would imagine," says Kelvin Chu, associate professor of physics and DeWitt's co-author, "that there has been evolutionary pressure on every species to adapt this motion in the myoglobin for their particular oxygen-binding needs."

"That's a testable hypothesis," Chu says. "What we would expect to see across species is that the tennis rackets are in different places or move different amounts."

DeWitt and Chu's work extends far beyond myoglobin. The two physicists see broad application of their new method in creating custom-crafted proteins.

"Once you know what these motions are and what the important atoms are," says Chu, "you can make mutants of proteins that have different binding attributes." And these different attributes have promise in developing new biotechnologies "ranging from blood substitutes to organic solar cells," he says.

Proteins are a cell's heavy laborers: hauling water, taking out the trash, carrying in the groceries -- and trillions of other tasks that make life. But how the shape of a protein determines its function remains one of the most vexing and important questions in the physics of biology.

Proteins are not the static, Lego-like objects you might see in an x-ray photograph in a biochemistry textbook. Instead, made from long chains of amino acids scrunched into various blobs and globs, a protein is always jumping between slightly different structural arrangements due to thermal motion of its atoms. Even a modest-sized protein like myoglobin has more possible arrangements of its atoms than there are stars in the universe. And each of these arrangements slightly changes a protein's function.

"But what are the important motions that control its function?" asks Chu.

"Relating the structure of a protein to what it is doing is the holy grail," he says. For myoglobin at least, the two UVM scientists seem to have brought the prize a lot closer to hand.

Their method -- called temperature derivative spectroscopy or TDS -- involves cooling myoglobin to as low as -450 degrees Fahrenheit, about 18 degrees above absolute zero, and then measuring its oxygen-binding process. At these chilly temperatures, each protein basically gets stuck in just one arrangement. These individual atomic arrangements can't be observed directly, but, using infrared light, a pack of myoglobin molecules does yield a kind of group portrait -- a summing, called a TDS surface -- of the position of all the proteins as they bind to the oxygen in carbon monoxide.

The Vermont scientists' innovation comes largely from what they have been able to do with this group portrait.

"This scenario is called an inverse problem," DeWitt notes, "we have measured the effect but want to determine the cause." Unfortunately, a bit like asking what two numbers add up to ten, there are many solutions.

But, usually, nature does not build wasteful structures -- and though the universe is undoubtedly complex, it does not seem given to capricious complexity. In other words, the scientific principle of parsimony -- what philosophy students encounter as Occam's Razor -- suggests that the least complex explanation is the most likely.

Applying a mathematical version of this idea from Bayesian statistics, called the principle of maximum entropy, DeWitt and Chu went looking for the simplest solution to the TDS surface created by their group of myoglobin molecules. And the answer: the motion of the distal histidine most simply explains how myoglobin regulates oxygen binding.

They followed this prediction by performing a computer simulation of the molecular dynamics of the distal histidine, which confirmed their interpretation.

"Will did a lot of this on his own," says Chu, "He took the data, and the analysis was done on a MacPro," plus some time on the National Science Foundation's high-performance computer network, the TeraGrid.

"He's a clever guy," says Chu.

Joshua Brown | EurekAlert!
Further information:

Further reports about: Myoglobin Occam's Razor Slicing proteins TDS UVM amino acid blue whale surfaces

More articles from Physics and Astronomy:

nachricht Move over, lasers: Scientists can now create holograms from neutrons, too
21.10.2016 | National Institute of Standards and Technology (NIST)

nachricht Finding the lightest superdeformed triaxial atomic nucleus
20.10.2016 | The Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences

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: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>