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From eons to seconds, proteins exploit the same forces
Date:8/13/2014

p>"If the selection temperature is too high in the sequence space, the search will give every possible sequence. But most of those wouldn't fold right. The low selection temperature tells us how important folding has been for evolution."

"If the selection temperature and the folding temperature were the same, it would tell us that proteins merely have to be thermodynamically stable," Wolynes said. "But when the selection temperature is lower than the folding temperature, the landscape actually has to be funneled."

"If proteins evolved to search for funnel-like sequences, the signature of this evolution will be seen projected on the sequences that we observe," Onuchic said. The close match between the sequence data and energetic structure analyses clearly show such a signature, he said, "and the importance of that is enormous."

"Basically, we now have two completely different sources of information, genomic and physical, that tell us how protein folding works," he said. Knowing how evolution did it should make it much faster for people to design proteins "because we can make a change in sequence and test its effect on folding very quickly," he said.

"Even if you don't fully solve a specific design problem, you can narrow it down to where experiments become much more practical," Onuchic said.

"Each of these methods has proved very useful and powerful when used in isolation, and we are just starting to learn what can be achieved when they are used together," said Nicholas Schafer, a Rice postdoctoral researcher and co-author. "I'm excited to be participating in what I think will be an explosion of research and applications centered around these kinds of ideas and techniques."

Faruck Morcos is the paper's lead author and Ryan Cheng is a co-author. Both are postdoctoral researchers at Rice. Onuchic is Rice's Harry C. and Olga K. Wiess Professor of Physics and Astronomy and co-director of the CTBP based at Rice's Bio
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Contact: David Ruth
david@rice.edu
713-348-6327
Rice University
Source:Eurekalert  

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