title: On the role of frustration in the energy landscapes of allosteric proteins.
abstract: 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.
authors.affiliation: Protein Physiology Lab, Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Buenos Aires, Argentina C1428EGA.
authors.forename: Diego U
authors.initials: DU
authors.lastname: Ferreiro
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hegler
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Komives
authors.forename: Peter G
authors.initials: PG
authors.lastname: Wolynes
mesh_terms: D000494:Allosteric Regulation; D000596:Amino Acids / Q000378:metabolism; D030562:Databases, Protein; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins