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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ftdoajarticles:oai:doaj.org/article:40704339941b41f99d0c1933e5fc335c 2023-05-15T13:56:29+02:00 A computational methodology to screen activities of enzyme variants. Martin R Hediger Luca De Vico Allan Svendsen Werner Besenmatter Jan H Jensen 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pone.0049849 https://doaj.org/article/40704339941b41f99d0c1933e5fc335c EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3524253?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0049849 https://doaj.org/article/40704339941b41f99d0c1933e5fc335c PLoS ONE, Vol 7, Iss 12, p e49849 (2012) Medicine R Science Q article 2012 ftdoajarticles https://doi.org/10.1371/journal.pone.0049849 2022-12-31T15:56:05Z 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. Article in Journal/Newspaper Antarc* Antarctica Directory of Open Access Journals: DOAJ Articles PLoS ONE 7 12 e49849 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Martin R Hediger Luca De Vico Allan Svendsen Werner Besenmatter Jan H Jensen A computational methodology to screen activities of enzyme variants. |
topic_facet |
Medicine R Science Q |
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. |
format |
Article in Journal/Newspaper |
author |
Martin R Hediger Luca De Vico Allan Svendsen Werner Besenmatter Jan H Jensen |
author_facet |
Martin R Hediger Luca De Vico Allan Svendsen Werner Besenmatter Jan H Jensen |
author_sort |
Martin R Hediger |
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. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pone.0049849 https://doaj.org/article/40704339941b41f99d0c1933e5fc335c |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
PLoS ONE, Vol 7, Iss 12, p e49849 (2012) |
op_relation |
http://europepmc.org/articles/PMC3524253?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0049849 https://doaj.org/article/40704339941b41f99d0c1933e5fc335c |
op_doi |
https://doi.org/10.1371/journal.pone.0049849 |
container_title |
PLoS ONE |
container_volume |
7 |
container_issue |
12 |
container_start_page |
e49849 |
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1766263995380006912 |