Scientists Unlock Secrets of Protein Folding

From Physorg.com.

A team led by biophysicist Jeremy Smith of the University of Tennessee and Oak Ridge National Laboratory 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.

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.

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.

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.

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.'"

"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."

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