ArticleProceedings of the National Academy of Sciences of the United States of America2019
Local frustration around enzyme active sites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- The protein-water H-bond network for bacterial response regulator REC domain activation.Journal of structural biology: X · 2026Article
- Trans-interface coupling in the tetrameric enzyme underlies allosteric control inJournal of structural biology: X · 2026Article
- Article
- Deconvolving mutation effects on protein stability and function with disentangled protein language models.bioRxiv : the preprint server for biology · 2026Article
- Probing the dark energy in the functional protein universe.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Binding Specificity and Local Frustration in Structure-based Drug Discovery.Current medicinal chemistry · 2026Review
- The AD3 locus of synaptotagmin-1 C2 domains modulates domain stability.Biophysical journal · 2025Article
- Frustration in physiology and molecular medicine.Molecular aspects of medicine · 2025Review
- Sequence-Sensitivity in Functional Synthetic Polymer Properties.Angewandte Chemie (International ed. in English) · 2025Article
- HyperMPNN-A general strategy to design thermostable proteins learned from hyperthermophiles.bioRxiv : the preprint server for biology · 2024Article
- Illuminating Protein Allostery by Chemically Accurate Contact Response Analysis (ChACRA).Journal of chemical theory and computation · 2024Article
- A contact-based analysis of local energetic frustration dynamics identifies key residues enabling RfaH fold-switch.Protein science : a publication of the Protein Society · 2024Article
- Frustraevo: a web server to localize and quantify the conservation of local energetic frustration in protein families.Nucleic acids research · 2024Article
- Residue coevolution and mutational landscape for OmpR and NarL response regulator subfamilies.Biophysical journal · 2024Article
- Conflicting Interfacial Electrostatic Interactions as a Design Principle to Modulate Long-Range Interdomain Communication.ACS bio & med chem Au · 2024Article
- Local energetic frustration conservation in protein families and superfamilies.Nature communications · 2023Article
- Fifty years of biophysics in Argentina.Biophysical reviews · 2023Article
- High-throughput thermal denaturation of tryptophanyl-tRNA synthetase combinatorial mutants reveals high-order energetic coupling determinants of conformational stability.Structural dynamics (Melville, N.Y.) · 2023Article
- Temperature-sensitive contacts in disordered loops tune enzyme I activity.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Solvation of theInternational journal of molecular sciences · 2022Article
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5 authors.
Funding
Abstract
Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. In agreement with previous hypotheses, the catalytic sites themselves are often highly frustrated regardless of the protein oligomeric state, overall topology, and enzymatic class. At the same time a secondary shell of more weakly frustrated interactions surrounds the catalytic site itself. We evaluate the conservation of these energetic signatures in various family members of major enzyme classes, showing that local frustration is evolutionarily more conserved than the primary structure itself.
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