Genetics, energetics, and allostery in proteins with randomized cores and surfaces
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- dc.contributor.author Escobedo, Albert
- dc.contributor.author Voigt, Gesa
- dc.contributor.author Faure, Andre J.
- dc.contributor.author Lehner, Ben, 1978-
- dc.date.accessioned 2025-09-29T13:06:14Z
- dc.date.available 2025-09-29T13:06:14Z
- dc.date.issued 2025
- dc.description.abstract A lack of systematic experimental data limits our understanding of protein evolution. In this study, we experimentally characterized proteins with randomized sequences. Vast numbers of amino acid combinations constitute stable protein cores and surfaces. However, alternative cores frequently disrupt protein function by indirect allosteric effects. Both protein stability and binding can be predicted using simple additive energy models with a small contribution from pairwise energetic couplings. Indeed, energy models trained on one protein can predict functional cores and surfaces across more than a billion years of evolution, with only rare energetic couplings that we experimentally identify limiting the transplantation of cores between highly diverged proteins. Our results reveal the simple energetic architecture of proteins and suggest that allostery is an important constraint on sequence evolution.
- dc.description.sponsorship This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 883742), “la Caixa” Foundation under the grant agreement HR21-00375, the Bettencourt Schueller Foundation, the AXA Research Fund (AXA Chair in Risk prediction in age-related diseases), the Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia (AGAUR, 2017 SGR 1322), and Wellcome (Grant reference: 220540/Z/20/A, 'Wellcome Sanger Institute Quinquennial Review 2021-2026').
- dc.format.mimetype application/pdf
- dc.identifier.citation Escobedo A, Voigt G, Faure AJ, Lehner B. Genetics, energetics, and allostery in proteins with randomized cores and surfaces. Science. 2025 Jul 24;389(6758):eadq3948. DOI: 10.1126/science.adq3948
- dc.identifier.doi http://dx.doi.org/10.1126/science.adq3948
- dc.identifier.issn 0036-8075
- dc.identifier.uri http://hdl.handle.net/10230/71290
- dc.language.iso eng
- dc.publisher American Association for the Advancement of Science (AAAS)
- dc.relation.ispartof Science. 2025 Jul 24;389(6758):eadq3948
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/883742
- dc.rights This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 2025 Jul 24;389(6758):eadq3948, DOI: 10.1126/science.adq3948
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.other Seqüència d'aminoàcids
- dc.subject.other Proteïnes--Anàlisi
- dc.title Genetics, energetics, and allostery in proteins with randomized cores and surfaces
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion