Scientists pioneer new method for watching proteins fold

The research was conducted by Feng Gai, professor in the Department of Chemistry in the School of Arts and Sciences, along with graduate students Arnaldo Serrano, also of Chemistry, and Robert Culik of the Department of Biochemistry and Molecular Biophysics at Penn’s Perelman School of Medicine. They collaborated with Michelle R. Bunagan of the College of New Jersey’s Department of Chemistry.

Their research was published in the international edition of the journal Angewandte Chemie, where it was featured on the cover and bestowed VIP (very important paper) status.

“One of the reasons that figuring out what happens when proteins fold is difficult is that we don’t have the equivalent of a high-speed camera that can capture the process, “ Gai said.  “If the process were slow, we could take multiple ‘pictures’ over time and see the mechanism at work. Unfortunately, no one has this capability; the folding occurs faster than the blink of an eye.”  

Gai’s team uses infrared spectroscopy — a technique that measures how much light different parts of a molecule absorbs — to analyze proteins’ structure and how this changes. In this case, the researchers looked at a model protein known as Trp-cage with an infrared laser setup.

In this experiment, Gai’s team used two lasers to study structural changes as a function of time. The first laser acts as the starting gun; by heating the molecule, it causes its structure to change. The second laser acts as the camera, following the motions of the protein’s constituent amino acids.
“The protein is made of different groups of atoms, and the different groups can be thought of as springs,” Gai said. “Each spring has a different frequency with which it moves back and forth, which is based on the mass of the atom on either end. If the mass is bigger, the spring oscillates slower. Our ‘camera’ can detect the speed of that motion and we can relate it to the atoms it is made of and how that segment of the protein chain moves.” 

Even in a simple protein like Trp-cage, however, there are many identical bonds, and the researchers need to be able to distinguish one from another in order to see which of them are moving while the protein folds. One strategy they used to get around this problem was to employ the molecular equivalent of a tracking device. 

“We use an amino acid with a carbon isotope marker,” Culik said. “If it’s incorporated into the protein correctly, we’ll know where it is.”

With a single carbon atom of the Trp-cage slightly heavier than the others, the research team can use its signature to infer the position of the other atoms as they fold. The researchers could then “tune” the frequency of their laser to match different parts of the protein, allowing them to isolate them in their analyses.  

Similar isotopes could be inserted in more complicated molecules, allowing their folds to also be viewed with infrared spectroscopy.  
“This technique enhances our structural resolution. It allows us to see which part is moving,” Gai said. “That would allow us to see exactly how a protein is misfolding in a disease, for example.”

Provided by University of Pennsylvania (news : web)

Laser pioneer or electrochemist for Nobel?

(AP) -- Americans William Moerner, Allen Bard and Richard Zare could be among the potential candidates when the Nobel Prize in chemistry is announced Wednesday.

Guessing a winner among scores of discoveries in such a broad field as chemistry is notoriously hard but that doesn't stop people from trying.

Recent discoveries are more or less ruled out because Nobel jurors look for research that has stood the test of time. Typically, Nobel winners have received plenty of other awards before they get the call from Stockholm.

Both Zare, a laser chemistry pioneer at Stanford University, and Bard, an electrochemistry expert of the University of Austin, Texas, have been decorated with multiple honors, including the Priestley Award, handed out by the American Chemical Society, and Israel's Wolf Prize.

Bard shared the latter in 2008 with Moerner, of Stanford University, for creating a new field of science: single-molecule spectroscopy and imaging.

Should the chemistry prize committee chose a woman, for a change, American Jacqueline Barton, of the California Institute of Technology, could get the nod for her work on the transport of electrons in DNA.

Only four women have won the chemistry prize since the awards were first handed out in 1901: French scientist Marie Curie (1911), her daughter Irene Joliot-Curie (1935), British chemist Dorothy Crowfoot Hodgkin (1964) and Ada Yonath of Israel (2009).

Other names that routinely pop up in Nobel speculation include Americans Stuart Schreiber and Gerald Crabtree for work that sheds light on how tiny molecules can be used on cell circuits and signaling pathways.

If the prize honors nanotechnology - the science dedicated to building materials from the molecular level - possible winners could include American Charles Lieber, British chemist James Fraser Stoddart or Japan's Sumio Iijima, who discovered carbon nanotubes in 1991.

The Nobel Prize in chemistry announcement will cap this year's science awards.

Immune system researchers Bruce Beutler of the U.S. and Frenchman Jules Hoffmann shared the medicine prize Monday with Canadian-born Ralph Steinman, who died three days before the announcement. U.S.-born scientists Saul Perlmutter, Brian Schmidt and Adam Riess won the physics prize on Tuesday for discovering that the universe is expanding at an accelerating pace.

Last year, the chemistry committee rewarded Japanese scientists Ei-ichi Negishi and Akira Suzuki and American Richard Heck for designing a technique to bind together carbon atoms, a key step in assembling the skeletons of organic compounds used in medicine, agriculture and electronics.

The 10 million kronor (US$1.4 million) Nobel Prizes are handed out every year on Dec. 10, the anniversary of award founder Alfred Nobel's death in 1896.

?2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Scientists pioneer new method for nanoribbon production

Research involving scientists from The University of Nottingham is pioneering a new method of studying and making molecules.

The work, reported in Nature Materials, could pave the way for the production of nanomaterials for use in a new generation of computers and data storage devices that are faster, smaller and more powerful.

The Nottingham research group, led by Dr Andrei Khlobystov in the University's School of Chemistry, specialise in the chemistry of nanomaterials and has been studying carbon nanotubes as containers for molecules and atoms.

Carbon nanotubes are remarkable nanostructures with a typical diameter of 1-2 nanometres, which is 80,000 times smaller than the thickness of a human hair. Over the past few years, the researchers have discovered that physical and chemical properties of molecules inserted into carbon nanotubes are very different to the properties of free molecules. This presents a powerful mechanism for manipulating the molecules, harnessing their functional properties, such as magnetic or optical, and for controlling their chemical reactivity.

The latest study is a collaboration between Dr Khlobystov's chemical nanoscientists, theoretical chemists based in the University's School of Chemistry and electron microscopists from Ulm University in German.

Working together, they have demonstrated that carbon nanotubes can be used as nanoscale chemical reactors and chemical reactions involving carbon and sulphur atoms held within a nanotube lead to the formation of atomically thin strips of carbon, known as graphene nanoribbon, decorated with sulphur atoms around the edge.

Dr Khlobystov said: "Graphene nanoribbons possess a wealth of interesting physical properties making them more suitable for applications in electronic and spintronic devices than the parent material graphene -- the discovery of which attracted the Nobel Prize for Physics last year for University of Manchester scientists Professors Andre Geim and Konstantin Novoselov.

"Nanoribbons are very difficult to make but the Nottingham team's strategy of confining chemical reactions at the nanoscale sparks spontaneous formation of these remarkable structures. The team has also discovered that nanoribbons -- far from being simple flat and linear structures -- possess an unprecedented helical twist that changes over time, giving scientists a way of controlling physical properties of the nanoribbon, such as electrical conductivity."

Devices based on nanoribbons could potentially be used as nano-switches, nano-actuators and nano-transistors integrated in computers or data storage devices.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of Nottingham.

Journal Reference:

A. Chuvilin, E. Bichoutskaia, M. C. Gimenez-Lopez, T. W. Chamberlain, G. A. Rance, N. Kuganathan, J. Biskupek, U. Kaiser, A. N. Khlobystov. Self-assembly of a sulphur-terminated graphene nanoribbon within a single-walled carbon nanotube. Nature Materials, 2011; DOI: 10.1038/nmat3082