Speeding Molecular Recognition by Using the Folding Funnel: The Fly-Casting Mechanism

Protein folding and binding are kindred processes. Many proteins in the cell are unfolded, so folding and function are coupled. This paper investigates how binding kinetics is influenced by the folding of a protein. We find that a relatively unstructured protein molecule can have a greater capture r...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 97; no. 16; pp. 8868 - 8873
Main Authors Shoemaker, Benjamin A., Portman, John J., Wolynes, Peter G.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 01.08.2000
National Acad Sciences
National Academy of Sciences
The National Academy of Sciences
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ISSN0027-8424
1091-6490
DOI10.1073/pnas.160259697

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Summary:Protein folding and binding are kindred processes. Many proteins in the cell are unfolded, so folding and function are coupled. This paper investigates how binding kinetics is influenced by the folding of a protein. We find that a relatively unstructured protein molecule can have a greater capture radius for a specific binding site than the folded state with its restricted conformational freedom. In this scenario of binding, the unfolded state binds weakly at a relatively large distance followed by folding as the protein approaches the binding site: the "fly-casting mechanism." We illustrate this scenario with the hypothetical kinetics of binding a single repressor molecule to a DNA site and find that the binding rate can be significantly enhanced over the rate of binding of a fully folded protein.
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Contributed by Peter G. Wolynes
To whom reprint requests should be addressed. E-mail: wolynes@uiuc.edu.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.160259697