In a study published Jan. 17 in the journal Molecular Cell, Hebert's team analyzes and documents the maturation of a cell taken from a flu virus. According to the team's findings, the position and location of the chaperones have evolved to optimize the folding process in the cell.

As reported in the Dec. 13 issue of the journal "Science," the Maryland team saw a protein take shape, a process called folding, in a series of steps, not one sudden motion, as had long been assumed to be the folding process.

"It's been thought that proteins had only two states, like an on-off switch," said Victor Munoz, the Maryland biochemistry professor who led the research. "Our discovery showed that there are proteins that act more like rheostats, gradually folding and unfolding."

"We have chosen to first look at a comparatively simple protein in water system consisting of about 18,000 atoms, called a 3-heilx bundle, that folds in a fairly simple way and relatively slowly, in about 10 microseconds," said Garcia. "Our calculation is based on Onuchic's 'funneling theory' of protein folding that looks at the 'energy landscape' of folding and finds that as the protein gets closer and closer to it's folded state it's energy gets lower and lower."

To confirm their predictions, the Stanford team asked Gruebele and Nguyen to conduct "laser temperature-jump experiments" at their Illinois lab. In this technique, an unfolded protein is pulsed with a laser, which heats the molecule just enough to cause it to bend into its native state. A fluorescent amino acid imbedded inside the molecule grows dimmer as the protein folds. Researchers use the changing fluorescence to measure folding events as they occur.

Trouble is, proteins don't make it at all easy to find out what they're doing.

From the perspective of experimental scientists like Gruebele, they're too small and they fold too fast – in a few millionths of a second – to observe in action using traditional techniques.

Protein folding is a process by which proteins assume precise three-dimensional shapes, which are necessary for them to carry out their function in the body. It is critical to understand this process because "a lot of diseases are caused by protein misfolding," Vijay Pande, assistant professor of chemistry and of structural biology at Stanford University and co-author of the research, told United Press International.

It ought to be possible to predict a protein's structure using computers to simulate how chains fold, knowing how amino acids tend to attract or repel one another. But, because many proteins contain hundreds or even thousands of amino acids, this problem is too complex for today's computers.

In Huntington's disease, for example, a mutated gene directs production of a protein with an increasing number of consecutive residues of the amino acid glutamine. When the number of residues expands past 40, the protein exhibits unusual biochemical properties, causing the protein to misfold. This results in a loss of function and protein aggregation -- in other words, disease.