Evolving folding

Naturally occurring small proteins fold in a single cooperative step. That is because evolution has selected for such behavior, say Alexander Watters, David Baker (University of Washington, Seattle, WA), and colleagues. They proved the rule by testing the exception: a computationally designed protein called Top7 with no evolutionary history and a far more complex folding strategy.

Previous tests relied on proteins that had been modified extensively but were still based on naturally occurring protein structures. These variants also folded rapidly, suggesting that cooperative folding might be intrinsic to any protein of a certain size and final stability.

The Washington group thought, however, that Top7 would make a more rigorous test substrate. They had computationally designed Top7 to be stable despite its completely novel fold and structure. Its folding,...