AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design

The recent success of AlphaFold2 (AF2) and other deep learning (DL) tools in accurately predicting the folded three-dimensional (3D) structure of proteins and enzymes has revolutionized the structural biology and protein design fields. The 3D structure indeed reveals key information on the arrangeme...

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Autores: Casadevall Franco, Guillem, Duran i Rebenaque, Cristina, Osuna Oliveras, Sílvia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/23543
Acceso en línea:http://hdl.handle.net/10256/23543
Access Level:acceso abierto
Palabra clave:Enzims -- Disseny
Enzymes -- Design
Proteïnes -- Conformació
Proteins -- Conformation
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spelling AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for DesignCasadevall Franco, GuillemDuran i Rebenaque, CristinaOsuna Oliveras, SílviaEnzims -- DissenyEnzymes -- DesignProteïnes -- ConformacióProteins -- ConformationThe recent success of AlphaFold2 (AF2) and other deep learning (DL) tools in accurately predicting the folded three-dimensional (3D) structure of proteins and enzymes has revolutionized the structural biology and protein design fields. The 3D structure indeed reveals key information on the arrangement of the catalytic machinery of enzymes and which structural elements gate the active site pocket. However, comprehending enzymatic activity requires a detailed knowledge of the chemical steps involved along the catalytic cycle and the exploration of the multiple thermally accessible conformations that enzymes adopt when in solution. In this Perspective, some of the recent studies showing the potential of AF2 in elucidating the conformational landscape of enzymes are provided. Selected examples of the key developments of AF2-based and DL methods for protein design are discussed, as well as a few enzyme design cases. These studies show the potential of AF2 and DL for allowing the routine computational design of efficient enzymesWe thank the Generalitat de Catalunya for the consolidated group TCBioSys (SGR 2021 00487) and grant projects PID2021-129034NB-I00 and PDC2022-133950-I00 funded by Spanish MICIN. S.O. is grateful for the funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC-2015-StG-679001, ERC-2022-POC-101112805, and ERC-2022-CoG-101088032) and the Human Frontier Science Program (HFSP) for project grant RGP0054/2020. G.C. was supported by a research grant from ERC-StG (ERC-2015-StG-679001) and HFSP RGP0054/2020. C.D. was supported by the Spanish MINECO for a PhD fellowship (PRE2019-089147)Open Access funding provided thanks to the CRUE-CSIC agreement with American Chemical Society (ACS)American Chemical Society (ACS)European CommissionAgencia Estatal de Investigación2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/23543Journal of the American Chemical Society (JACS), 2023, vol. 3, núm. 6, p. 1554-1562Articles publicats (D-Q)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1021/jacsau.3c00188info:eu-repo/semantics/altIdentifier/issn/0002-7863info:eu-repo/semantics/altIdentifier/eissn/1520-5126PID2021-129034NB-I00PDC2022-133950-I00info:eu-repo/grantAgreement/EC/H2020/679001info:eu-repo/grantAgreement/EC/HE/101112805info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-129034NB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PDC2022-133950-I00info:eu-repo/grantAgreement/EC/HE/101088032Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/235432026-05-29T05:05:01Z
dc.title.none.fl_str_mv AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design
title AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design
spellingShingle AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design
Casadevall Franco, Guillem
Enzims -- Disseny
Enzymes -- Design
Proteïnes -- Conformació
Proteins -- Conformation
title_short AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design
title_full AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design
title_fullStr AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design
title_full_unstemmed AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design
title_sort AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design
dc.creator.none.fl_str_mv Casadevall Franco, Guillem
Duran i Rebenaque, Cristina
Osuna Oliveras, Sílvia
author Casadevall Franco, Guillem
author_facet Casadevall Franco, Guillem
Duran i Rebenaque, Cristina
Osuna Oliveras, Sílvia
author_role author
author2 Duran i Rebenaque, Cristina
Osuna Oliveras, Sílvia
author2_role author
author
dc.contributor.none.fl_str_mv European Commission
Agencia Estatal de Investigación
dc.subject.none.fl_str_mv Enzims -- Disseny
Enzymes -- Design
Proteïnes -- Conformació
Proteins -- Conformation
topic Enzims -- Disseny
Enzymes -- Design
Proteïnes -- Conformació
Proteins -- Conformation
description The recent success of AlphaFold2 (AF2) and other deep learning (DL) tools in accurately predicting the folded three-dimensional (3D) structure of proteins and enzymes has revolutionized the structural biology and protein design fields. The 3D structure indeed reveals key information on the arrangement of the catalytic machinery of enzymes and which structural elements gate the active site pocket. However, comprehending enzymatic activity requires a detailed knowledge of the chemical steps involved along the catalytic cycle and the exploration of the multiple thermally accessible conformations that enzymes adopt when in solution. In this Perspective, some of the recent studies showing the potential of AF2 in elucidating the conformational landscape of enzymes are provided. Selected examples of the key developments of AF2-based and DL methods for protein design are discussed, as well as a few enzyme design cases. These studies show the potential of AF2 and DL for allowing the routine computational design of efficient enzymes
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/23543
url http://hdl.handle.net/10256/23543
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/jacsau.3c00188
info:eu-repo/semantics/altIdentifier/issn/0002-7863
info:eu-repo/semantics/altIdentifier/eissn/1520-5126
PID2021-129034NB-I00
PDC2022-133950-I00
info:eu-repo/grantAgreement/EC/H2020/679001
info:eu-repo/grantAgreement/EC/HE/101112805
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-129034NB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PDC2022-133950-I00
info:eu-repo/grantAgreement/EC/HE/101088032
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society (ACS)
publisher.none.fl_str_mv American Chemical Society (ACS)
dc.source.none.fl_str_mv Journal of the American Chemical Society (JACS), 2023, vol. 3, núm. 6, p. 1554-1562
Articles publicats (D-Q)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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