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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ftdatacite:10.48550/arxiv.1203.2950 2023-05-15T13:53:56+02:00 A Computational Methodology to Screen Activities of Enzyme Variants Hediger, Martin R. De Vico, Luca Svendsen, Allan Besenmatter, Werner Jensen, Jan H. 2012 https://dx.doi.org/10.48550/arxiv.1203.2950 https://arxiv.org/abs/1203.2950 unknown arXiv https://dx.doi.org/10.1371/journal.pone.0049849 arXiv.org perpetual, non-exclusive license http://arxiv.org/licenses/nonexclusive-distrib/1.0/ Chemical Physics physics.chem-ph FOS Physical sciences article-journal Article ScholarlyArticle Text 2012 ftdatacite https://doi.org/10.48550/arxiv.1203.2950 https://doi.org/10.1371/journal.pone.0049849 2022-04-01T14:02:56Z 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 Candida Antarctica lipase B (CalB) enzyme. The barrier heights are estimated using adiabatic mapping and are shown to give barrier heights to within 3kcal/mol of B3LYP/6-31G(d)//RHF/3-21G results for a small model system. Relatively strict convergence criteria (0.5kcal/(molÅ)), long NDDO cutoff distances within the MOZYME method (15Å) and single point evaluations using conventional PM6 are needed for reliable results. The generation of mutant structure 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. Text Antarc* Antarctica DataCite Metadata Store (German National Library of Science and Technology) |
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DataCite Metadata Store (German National Library of Science and Technology) |
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Chemical Physics physics.chem-ph FOS Physical sciences |
spellingShingle |
Chemical Physics physics.chem-ph FOS Physical sciences Hediger, Martin R. De Vico, Luca Svendsen, Allan Besenmatter, Werner Jensen, Jan H. A Computational Methodology to Screen Activities of Enzyme Variants |
topic_facet |
Chemical Physics physics.chem-ph FOS Physical sciences |
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 Candida Antarctica lipase B (CalB) enzyme. The barrier heights are estimated using adiabatic mapping and are shown to give barrier heights to within 3kcal/mol of B3LYP/6-31G(d)//RHF/3-21G results for a small model system. Relatively strict convergence criteria (0.5kcal/(molÅ)), long NDDO cutoff distances within the MOZYME method (15Å) and single point evaluations using conventional PM6 are needed for reliable results. The generation of mutant structure 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 |
Text |
author |
Hediger, Martin R. De Vico, Luca Svendsen, Allan Besenmatter, Werner Jensen, Jan H. |
author_facet |
Hediger, Martin R. De Vico, Luca Svendsen, Allan Besenmatter, Werner Jensen, Jan H. |
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 |
publisher |
arXiv |
publishDate |
2012 |
url |
https://dx.doi.org/10.48550/arxiv.1203.2950 https://arxiv.org/abs/1203.2950 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
https://dx.doi.org/10.1371/journal.pone.0049849 |
op_rights |
arXiv.org perpetual, non-exclusive license http://arxiv.org/licenses/nonexclusive-distrib/1.0/ |
op_doi |
https://doi.org/10.48550/arxiv.1203.2950 https://doi.org/10.1371/journal.pone.0049849 |
_version_ |
1766259417503760384 |