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Scientists at the University of Wisconsin-Milwaukee have demonstrated a new, high-speed method of mapping the changing atomic structures of proteins as they go about their crucial work, a development that paves the way for inquiries into some of the fundamental questions in biology and medicine.

"We want to understand the molecular basis of life, for example how plants use solar energy to split water, how cells develop to a full-grown organism, how we think, even how we develop consciousness, the ability to reason and have empathy," said Marius Schmidt, a UWM physics professor and the senior author of the new study, which appears in the journal Science.

Another key question the work may help researchers to ask: What is the molecular origin of cancer?

William Royer, professor of Medicine at the University of Massachusetts School of Medicine, called the new paper "a tour de force" that first will help scientists better understand proteins, and eventually enable pharmaceutical companies to design better drugs. He said understanding proteins should also shed new light on the growing problem of resistance to antibiotics and other drugs.

Schmidt led the project — "a massive effort" in his words — which included experiments at the SLAC National Accelerator Laboratory in California and work by three dozen scientists in the U.S., England and Germany. The crucial experiments took place over about four days this past summer, but followed four years of preparation. Funding came from a major grant awarded last year by the National Science Foundation; UWM's share totaled almost $4 million.

Proteins are the workhorse molecules necessary for virtually every human action from breathing to thinking; our bodies contain about 100,000 different kinds. Many diseases, including cystic fibrosis and sickle cell anemia, stem from the failure to manufacture a protein correctly, making them exceptionally valuable targets for drug development.

In the late 1950s, scientists mapped the first three-dimensional structure of a protein, myoglobin, work recognized with the Nobel Prize in chemistry in 1962. Although scientists now know the arrangement of atoms in thousands of proteins, the vast majority of those are proteins that are not in motion.

"You freeze the motions of life basically," Schmidt said. "What is missing is the motion."

That leaves scientists in the position of deducing what a protein does from a picture in which the protein isn't doing anything. Schmidt compares the task to staring at a construction vehicle parked on an empty lot and trying to figure out what the vehicle actually does.

Being able to map out the changes in atomic structure becomes important in examining the class of proteins called enzymes.

"Enzymes perpetuate the functions of life," Schmidt said. "We move with enzymes."

For example, enzymes help us to digest meat by acting a little like a butcher's knife at the molecular level. The enzymes cleave the chemical bonds that hold the meat together.

To get these detailed and fluid pictures of the changing structures of proteins, the scientists used a two stage technique called "pump and probe." They fire an optical laser at a crystal the size of a bacterium to get the atoms moving. Then they bombard the crystal with X-rays and map the diffraction of the atoms. Faster than the blink of an eye, the experiment produces and documents protein changes.

Previously, another method had been used to map changes in the atomic structure of moving proteins, but the method used by the UWM researchers and their colleagues is faster by five orders of magnitude.

"We are the first to show that this method works," Schmidt said.

The other institutions that took part in the study were: Arizona State University, State University of New York at Buffalo, University of Chicago, Imperial College in London, Lawrence Livermore National Laboratory, Stanford Linear Accelerator and Deutsches Elektronen-Synchrotron.