Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approach

The three-dimensional structure of the enzymes provides very relevant information on the arrangement of the catalytic machinery and structural elements gating the active site pocket. The recent success of the neural network Alphafold2 in predicting the folded structure of proteins from the primary s...

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Detalles Bibliográficos
Autores: Casadevall Franco, Guillem, Duran i Rebenaque, Cristina, Estévez Gay, Miquel, Osuna Oliveras, Sílvia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
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:10256/21725
Acceso en línea:http://hdl.handle.net/10256/21725
Access Level:acceso abierto
Palabra clave:Enzims
Enzymes
Dinàmica molecular -- Simulació per ordinador
Molecular dynamics -- Computer simulation
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spelling Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approachCasadevall Franco, GuillemDuran i Rebenaque, CristinaEstévez Gay, MiquelOsuna Oliveras, SílviaEnzimsEnzymesDinàmica molecular -- Simulació per ordinadorMolecular dynamics -- Computer simulationThe three-dimensional structure of the enzymes provides very relevant information on the arrangement of the catalytic machinery and structural elements gating the active site pocket. The recent success of the neural network Alphafold2 in predicting the folded structure of proteins from the primary sequence with high levels of accuracy has revolutionized the protein design field. However, the application of Alphafold2 for understanding and engineering function directly from the obtained single static picture is not straightforward. Indeed, understanding enzymatic function requires the exploration of the ensemble of thermally accessible conformations that enzymes adopt in solution. In the present study, we evaluate the potential of Alphafold2 in assessing the effect of the mutations on the conformational landscape of the beta subunit of tryptophan synthase (TrpB). Specifically, we develop a template-based Alphafold2 approach for estimating the conformational heterogeneity of several TrpB enzymes, which is needed for enhanced stand-alone activity. Our results show the potential of Alphafold2, especially if combined with molecular dynamics simulations, for elucidating the changes induced by mutation in the conformational landscapes at a rather reduced computational cost, thus revealing its plausible application in computational enzyme designH2020 European Research Council. Grant Number: ERC-2015-StG-679001 Human Frontier Science Program. Grant Number: RGP0054/2020 Ministerio de Ciencia e Innovación. Grant Number: PGC2018-102192-B-I00Open Access funding provided thanks to the CRUE-CSIC agreement with WileyWileyEuropean CommissionAgencia Estatal de Investigación2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/21725Protein Science, 2022, vol. 31, núm. 10, p. e4426Articles 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/10.1002/pro.4426info:eu-repo/semantics/altIdentifier/issn/0961-8368info:eu-repo/semantics/altIdentifier/eissn/1469-896XPGC2018-102192-B-I00info:eu-repo/grantAgreement/EC/H2020/679001info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-102192-B-I00Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/217252026-05-29T05:05:01Z
dc.title.none.fl_str_mv Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approach
title Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approach
spellingShingle Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approach
Casadevall Franco, Guillem
Enzims
Enzymes
Dinàmica molecular -- Simulació per ordinador
Molecular dynamics -- Computer simulation
title_short Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approach
title_full Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approach
title_fullStr Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approach
title_full_unstemmed Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approach
title_sort Estimating conformational heterogeneity of tryptophan synthase with a template-based Alphafold2 approach
dc.creator.none.fl_str_mv Casadevall Franco, Guillem
Duran i Rebenaque, Cristina
Estévez Gay, Miquel
Osuna Oliveras, Sílvia
author Casadevall Franco, Guillem
author_facet Casadevall Franco, Guillem
Duran i Rebenaque, Cristina
Estévez Gay, Miquel
Osuna Oliveras, Sílvia
author_role author
author2 Duran i Rebenaque, Cristina
Estévez Gay, Miquel
Osuna Oliveras, Sílvia
author2_role author
author
author
dc.contributor.none.fl_str_mv European Commission
Agencia Estatal de Investigación
dc.subject.none.fl_str_mv Enzims
Enzymes
Dinàmica molecular -- Simulació per ordinador
Molecular dynamics -- Computer simulation
topic Enzims
Enzymes
Dinàmica molecular -- Simulació per ordinador
Molecular dynamics -- Computer simulation
description The three-dimensional structure of the enzymes provides very relevant information on the arrangement of the catalytic machinery and structural elements gating the active site pocket. The recent success of the neural network Alphafold2 in predicting the folded structure of proteins from the primary sequence with high levels of accuracy has revolutionized the protein design field. However, the application of Alphafold2 for understanding and engineering function directly from the obtained single static picture is not straightforward. Indeed, understanding enzymatic function requires the exploration of the ensemble of thermally accessible conformations that enzymes adopt in solution. In the present study, we evaluate the potential of Alphafold2 in assessing the effect of the mutations on the conformational landscape of the beta subunit of tryptophan synthase (TrpB). Specifically, we develop a template-based Alphafold2 approach for estimating the conformational heterogeneity of several TrpB enzymes, which is needed for enhanced stand-alone activity. Our results show the potential of Alphafold2, especially if combined with molecular dynamics simulations, for elucidating the changes induced by mutation in the conformational landscapes at a rather reduced computational cost, thus revealing its plausible application in computational enzyme design
publishDate 2022
dc.date.none.fl_str_mv 2022
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/10256/21725
url http://hdl.handle.net/10256/21725
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.4426
info:eu-repo/semantics/altIdentifier/issn/0961-8368
info:eu-repo/semantics/altIdentifier/eissn/1469-896X
PGC2018-102192-B-I00
info:eu-repo/grantAgreement/EC/H2020/679001
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-102192-B-I00
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Protein Science, 2022, vol. 31, núm. 10, p. e4426
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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