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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Main Authors: Martin R Hediger, Luca De Vico, Allan Svendsen, Werner Besenmatter, Jan H Jensen
Format: Article in Journal/Newspaper
Language:unknown
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Online Access: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
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spelling 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)
institution Open Polar
collection RePEc (Research Papers in Economics)
op_collection_id ftrepec
language unknown
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
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