A Computational Methodology to Screen Activities of Enzyme Variants
We present a fast computational method to efficiently screen enzyme activity. In the presented method, the effect of mutations on the barrier height of an enzyme-catalysed reaction can be computed within 24 hours on roughly 10 processors. The methodology is based on the PM6 and MOZYME methods as imp...
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ftunivsiena:oai:usiena-air.unisi.it:11365/1006776 2024-04-21T07:47:39+00:00 A Computational Methodology to Screen Activities of Enzyme Variants Hediger, Martin R. Svendsen, Allan Besenmatter, Werner Jensen, Jan H. DE VICO, LUCA Hediger, Martin R. DE VICO, Luca Svendsen, Allan Besenmatter, Werner Jensen, Jan H. 2012 ELETTRONICO http://hdl.handle.net/11365/1006776 https://doi.org/10.1371/journal.pone.0049849 http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0049849&representation=PDF eng eng info:eu-repo/semantics/altIdentifier/pmid/23284627 info:eu-repo/semantics/altIdentifier/wos/WOS:000312435900004 volume:7 issue:12 firstpage:e49849 journal:PLOS ONE http://hdl.handle.net/11365/1006776 doi:10.1371/journal.pone.0049849 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84871279009 http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0049849&representation=PDF Biocatalysi Computational Biology Enzyme Assay Fungal Protein Lipase Models Molecular Mutation Protein Conformation Thermodynamic Time Factor Agricultural and Biological Sciences (all) Biochemistry Genetics and Molecular Biology (all) Medicine (all) info:eu-repo/semantics/article 2012 ftunivsiena https://doi.org/10.1371/journal.pone.0049849 2024-03-28T00:46:28Z We present a fast computational method to efficiently screen enzyme activity. In the presented method, the effect of mutations on the barrier height of an enzyme-catalysed reaction can be computed within 24 hours on roughly 10 processors. The methodology is based on the PM6 and MOZYME methods as implemented in MOPAC2009, and is tested on the first step of the amide hydrolysis reaction catalyzed by the Candida Antarctica lipase B (CalB) enzyme. The barrier heights are estimated using adiabatic mapping and shown to give barrier heights to within 3 kcal/mol of B3LYP/6-31G(d)//RHF/3-21G results for a small model system. Relatively strict convergence criteria (0.5 kcal/(molÅ)), long NDDO cutoff distances within the MOZYME method (15 Å) and single point evaluations using conventional PM6 are needed for reliable results. The generation of mutant structures and subsequent setup of the semiempirical calculations are automated so that the effect on barrier heights can be estimated for hundreds of mutants in a matter of weeks using high performance computing. © 2012 Hediger et al. Article in Journal/Newspaper Antarc* Antarctica Università degli Studi di Siena: USiena air PLoS ONE 7 12 e49849 |
institution |
Open Polar |
collection |
Università degli Studi di Siena: USiena air |
op_collection_id |
ftunivsiena |
language |
English |
topic |
Biocatalysi Computational Biology Enzyme Assay Fungal Protein Lipase Models Molecular Mutation Protein Conformation Thermodynamic Time Factor Agricultural and Biological Sciences (all) Biochemistry Genetics and Molecular Biology (all) Medicine (all) |
spellingShingle |
Biocatalysi Computational Biology Enzyme Assay Fungal Protein Lipase Models Molecular Mutation Protein Conformation Thermodynamic Time Factor Agricultural and Biological Sciences (all) Biochemistry Genetics and Molecular Biology (all) Medicine (all) Hediger, Martin R. Svendsen, Allan Besenmatter, Werner Jensen, Jan H. DE VICO, LUCA A Computational Methodology to Screen Activities of Enzyme Variants |
topic_facet |
Biocatalysi Computational Biology Enzyme Assay Fungal Protein Lipase Models Molecular Mutation Protein Conformation Thermodynamic Time Factor Agricultural and Biological Sciences (all) Biochemistry Genetics and Molecular Biology (all) Medicine (all) |
description |
We present a fast computational method to efficiently screen enzyme activity. In the presented method, the effect of mutations on the barrier height of an enzyme-catalysed reaction can be computed within 24 hours on roughly 10 processors. The methodology is based on the PM6 and MOZYME methods as implemented in MOPAC2009, and is tested on the first step of the amide hydrolysis reaction catalyzed by the Candida Antarctica lipase B (CalB) enzyme. The barrier heights are estimated using adiabatic mapping and shown to give barrier heights to within 3 kcal/mol of B3LYP/6-31G(d)//RHF/3-21G results for a small model system. Relatively strict convergence criteria (0.5 kcal/(molÅ)), long NDDO cutoff distances within the MOZYME method (15 Å) and single point evaluations using conventional PM6 are needed for reliable results. The generation of mutant structures and subsequent setup of the semiempirical calculations are automated so that the effect on barrier heights can be estimated for hundreds of mutants in a matter of weeks using high performance computing. © 2012 Hediger et al. |
author2 |
Hediger, Martin R. DE VICO, Luca Svendsen, Allan Besenmatter, Werner Jensen, Jan H. |
format |
Article in Journal/Newspaper |
author |
Hediger, Martin R. Svendsen, Allan Besenmatter, Werner Jensen, Jan H. DE VICO, LUCA |
author_facet |
Hediger, Martin R. Svendsen, Allan Besenmatter, Werner Jensen, Jan H. DE VICO, LUCA |
author_sort |
Hediger, Martin R. |
title |
A Computational Methodology to Screen Activities of Enzyme Variants |
title_short |
A Computational Methodology to Screen Activities of Enzyme Variants |
title_full |
A Computational Methodology to Screen Activities of Enzyme Variants |
title_fullStr |
A Computational Methodology to Screen Activities of Enzyme Variants |
title_full_unstemmed |
A Computational Methodology to Screen Activities of Enzyme Variants |
title_sort |
computational methodology to screen activities of enzyme variants |
publishDate |
2012 |
url |
http://hdl.handle.net/11365/1006776 https://doi.org/10.1371/journal.pone.0049849 http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0049849&representation=PDF |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
info:eu-repo/semantics/altIdentifier/pmid/23284627 info:eu-repo/semantics/altIdentifier/wos/WOS:000312435900004 volume:7 issue:12 firstpage:e49849 journal:PLOS ONE http://hdl.handle.net/11365/1006776 doi:10.1371/journal.pone.0049849 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84871279009 http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0049849&representation=PDF |
op_doi |
https://doi.org/10.1371/journal.pone.0049849 |
container_title |
PLoS ONE |
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7 |
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