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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ftrepec:oai:RePEc:plo:pone00:0049849 2024-04-14T08:03:01+00:00 A Computational Methodology to Screen Activities of Enzyme Variants Martin R Hediger Luca De Vico Allan Svendsen Werner Besenmatter Jan H Jensen https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0049849 https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0049849&type=printable unknown https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0049849 https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0049849&type=printable article ftrepec 2024-03-19T10:26:13Z 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 RePEc (Research Papers in Economics) |
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Open Polar |
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RePEc (Research Papers in Economics) |
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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 |
spellingShingle |
Martin R Hediger Luca De Vico Allan Svendsen Werner Besenmatter Jan H Jensen A Computational Methodology to Screen Activities of Enzyme Variants |
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 |
url |
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0049849 https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0049849&type=printable |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0049849 https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0049849&type=printable |
_version_ |
1796319438292647936 |