Protein Engineering, Vol. 12, No. 9, 713-720,
September 1999
© 1999 Oxford University Press
Folding funnels and binding mechanisms
1 Laboratory of Experimental and Computational Biology and 2 Intramural Research Support Program—SAIC, Laboratory of Experimental and Computational Biology, NCI–FCRDC, Frederick, MD 21702, USA and 3 Sackler Institute of Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
The long-held views on lock-and-key versus induced fit in binding arose from the notion that a protein exists in a single, most stable conformation, dictated by its sequence. However, in solution proteins exist in a range of conformations, which may be described by statistical mechanical laws and their populations follow statistical distributions. Upon binding, the equilibrium will shift in favor of the bound conformation from the ensemble of conformations around the bottom of the folding funnel. Hence here we extend the implications and the usefulness of the folding funnel concept to explain fundamental binding mechanisms.
Keywords: binding/conformational ensembles/energy landscape/folding/funnels/lock-and-key vs induced fit/misfolding
4 To whom correspondence should be addressed, at the US address. E-mail: ruthn{at}ncifcrf.gov
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