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Curr Opin Struct Biol. 2007 Jun;17(3):342-6. Epub 2007 Jun 14.

The protein folding problem: when will it be solved?

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Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA.


The protein folding problem can be viewed as three different problems: defining the thermodynamic folding code; devising a good computational structure prediction algorithm; and answering Levinthal's question regarding the kinetic mechanism of how proteins can fold so quickly. Once regarded as a grand challenge, protein folding has seen much progress in recent years. Folding codes are now being used to successfully design proteins and non-biological foldable polymers; aided by the Critical Assessment of Techniques for Structure Prediction (CASP) competition, protein structure prediction has now become quite good. Even the once-challenging Levinthal puzzle now seems to have an answer--a protein can avoid searching irrelevant conformations and fold quickly by making local independent decisions first, followed by non-local global decisions later.

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