On the role of frustration in the energy landscapes of allosteric proteins

Natural protein domains must be sufficiently stable to fold but often need to be locally unstable to function. Overall, strong energetic conflicts are minimized in native states satisfying the principle of minimal frustration. Local violations of this principle open up possibilities to form the comp...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-03, Vol.108 (9), p.3499-3503
Main Authors: Ferreiro, Diego U, Hegler, Joseph A, Komives, Elizabeth A, Wolynes, Peter G
Format: Article
Language:English
Subjects:
Allosteric Regulation
Amino Acids - metabolism
Biochemistry
Biological Sciences
Cots
Databases, Protein
Energy
Free energy
Frustration
Kinetics
Models, Molecular
Molecules
Monomers
Physical Sciences
Protein folding
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins
Proteins - chemistry
Proteins - metabolism
Reaction kinetics
Statistical mechanics
Thermodynamics
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Summary:Natural protein domains must be sufficiently stable to fold but often need to be locally unstable to function. Overall, strong energetic conflicts are minimized in native states satisfying the principle of minimal frustration. Local violations of this principle open up possibilities to form the complex multifunnel energy landscapes needed for large-scale conformational changes. We survey the local frustration patterns of allosteric domains and show that the regions that reconfigure are often enriched in patches of highly frustrated interactions, consistent both with the idea that these locally frustrated regions may act as specific hinges or that proteins may "crack" in these locations. On the other hand, the symmetry of multimeric protein assemblies allows near degeneracy by reconfiguring while maintaining minimally frustrated interactions. We also anecdotally examine some specific examples of complex conformational changes and speculate on the role of frustration in the kinetics of allosteric change.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1018980108