Localizing frustration in native proteins and protein assemblies

*Center for Theoretical Biological Physics and
^†Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0365

Contributed by Peter G. Wolynes, October 17, 2007 (received for review September 28, 2007)

Abstract

We propose a method of quantifying the degree of frustration manifested by spatially local interactions in protein biomolecules. This method of localization smoothly generalizes the global criterion for an energy landscape to be funneled to the native state, which is in keeping with the principle of minimal frustration. A survey of the structural database shows that natural proteins are multiply connected by a web of local interactions that are individually minimally frustrated. In contrast, highly frustrated interactions are found clustered on the surface, often near binding sites. These binding sites become less frustrated upon complex formation.

Footnotes

^‡To whom correspondence should be addressed. E-mail: pwolynes{at}ucsd.edu
Author contributions: D.U.F., J.A.H., E.A.K., and P.G.W. designed research; D.U.F. and J.A.H. performed research; D.U.F., J.A.H., E.A.K., and P.G.W. analyzed data; and D.U.F. and P.G.W. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0709915104/DC1.