Molecular insights into the promiscuity of serine hydrolases. Towards a computationally guided protocol for the redesign of enzymes
Compendi d'articles, Doctorat internacional Two serine hydrolases, Candida antarctica Lipase B (CALB) and para-nitrobenzyl (Bs2) esterase from Bacillus subtilis, were used as a model to study enzyme promiscuity through QM/MM methods and experimental enzymes kinetics. Both, the catalytic and the...
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Universitat Jaume I
2022
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ftunivjaumeirep:oai:repositori.uji.es:10803/673316 2024-09-09T19:04:59+00:00 Molecular insights into the promiscuity of serine hydrolases. Towards a computationally guided protocol for the redesign of enzymes Galmés Ordinas, Miquel Àngel Moliner Ibáñez, Vicente Swiderek, Katarzyna Patrycja Martí Forés, Sergio Universitat Jaume I. Escola de Doctorat 2022-01-28T11:57:31Z http://hdl.handle.net/10803/673316 https://doi.org/10.6035/14122.2022.725777 eng eng Universitat Jaume I http://hdl.handle.net/10803/673316 http://dx.doi.org/10.6035/14122.2022.725777 L'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess TDX (Tesis Doctorals en Xarxa) Enzyme catalysis QM/MM Enzyme promiscuity Rational design Ciències naturals químiques físiques i matemàtiques 544 577 info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion 2022 ftunivjaumeirep https://doi.org/10.6035/14122.2022.725777 2024-06-18T14:26:31Z Compendi d'articles, Doctorat internacional Two serine hydrolases, Candida antarctica Lipase B (CALB) and para-nitrobenzyl (Bs2) esterase from Bacillus subtilis, were used as a model to study enzyme promiscuity through QM/MM methods and experimental enzymes kinetics. Both, the catalytic and the substrate promiscuity were studied. The hydrolysis of amides and the epoxidation of alkenes catalyzed by CALB were explored. Moreover, a computational scheme for the redesign of the Bs2 was also proposed. The electrostatic environment around the active site was analyzed and a map of structural determinants in the vicinity of the active site pocket was done using 3D Convolutional Neural Networks. The proposed computationally guided protocol for the mutagenesis of enzymes based on the detailed analysis of the electrostatic environment of two structurally aligned trajectories using rotation quaternions was applied. A new mutant variant of the Bs2 was suggested as an improved catalytic variant by combining the best electrostatic features of both enzymes. Programa de Doctorat en Química Teòrica i Modelització Computacional Doctoral or Postdoctoral Thesis Antarc* Antarctica Repositori Universitat Jaume I (Repositorio UJI) |
institution |
Open Polar |
collection |
Repositori Universitat Jaume I (Repositorio UJI) |
op_collection_id |
ftunivjaumeirep |
language |
English |
topic |
Enzyme catalysis QM/MM Enzyme promiscuity Rational design Ciències naturals químiques físiques i matemàtiques 544 577 |
spellingShingle |
Enzyme catalysis QM/MM Enzyme promiscuity Rational design Ciències naturals químiques físiques i matemàtiques 544 577 Galmés Ordinas, Miquel Àngel Molecular insights into the promiscuity of serine hydrolases. Towards a computationally guided protocol for the redesign of enzymes |
topic_facet |
Enzyme catalysis QM/MM Enzyme promiscuity Rational design Ciències naturals químiques físiques i matemàtiques 544 577 |
description |
Compendi d'articles, Doctorat internacional Two serine hydrolases, Candida antarctica Lipase B (CALB) and para-nitrobenzyl (Bs2) esterase from Bacillus subtilis, were used as a model to study enzyme promiscuity through QM/MM methods and experimental enzymes kinetics. Both, the catalytic and the substrate promiscuity were studied. The hydrolysis of amides and the epoxidation of alkenes catalyzed by CALB were explored. Moreover, a computational scheme for the redesign of the Bs2 was also proposed. The electrostatic environment around the active site was analyzed and a map of structural determinants in the vicinity of the active site pocket was done using 3D Convolutional Neural Networks. The proposed computationally guided protocol for the mutagenesis of enzymes based on the detailed analysis of the electrostatic environment of two structurally aligned trajectories using rotation quaternions was applied. A new mutant variant of the Bs2 was suggested as an improved catalytic variant by combining the best electrostatic features of both enzymes. Programa de Doctorat en Química Teòrica i Modelització Computacional |
author2 |
Moliner Ibáñez, Vicente Swiderek, Katarzyna Patrycja Martí Forés, Sergio Universitat Jaume I. Escola de Doctorat |
format |
Doctoral or Postdoctoral Thesis |
author |
Galmés Ordinas, Miquel Àngel |
author_facet |
Galmés Ordinas, Miquel Àngel |
author_sort |
Galmés Ordinas, Miquel Àngel |
title |
Molecular insights into the promiscuity of serine hydrolases. Towards a computationally guided protocol for the redesign of enzymes |
title_short |
Molecular insights into the promiscuity of serine hydrolases. Towards a computationally guided protocol for the redesign of enzymes |
title_full |
Molecular insights into the promiscuity of serine hydrolases. Towards a computationally guided protocol for the redesign of enzymes |
title_fullStr |
Molecular insights into the promiscuity of serine hydrolases. Towards a computationally guided protocol for the redesign of enzymes |
title_full_unstemmed |
Molecular insights into the promiscuity of serine hydrolases. Towards a computationally guided protocol for the redesign of enzymes |
title_sort |
molecular insights into the promiscuity of serine hydrolases. towards a computationally guided protocol for the redesign of enzymes |
publisher |
Universitat Jaume I |
publishDate |
2022 |
url |
http://hdl.handle.net/10803/673316 https://doi.org/10.6035/14122.2022.725777 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
TDX (Tesis Doctorals en Xarxa) |
op_relation |
http://hdl.handle.net/10803/673316 http://dx.doi.org/10.6035/14122.2022.725777 |
op_rights |
L'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.6035/14122.2022.725777 |
_version_ |
1809818983211204608 |