In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB

In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB

Our previously presented method for high throughput computational screening of mutant activity (Hediger et al., 2012) is benchmarked against experimentally measured amidase activity for 22 mutants of Candida antarctica lipase B (CalB). Using an appropriate cutoff criterion for the computed barriers,...

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Main Authors: Martin R. Hediger, Luca De Vico, Julie B. Rannes, Christian Jäckel, Werner Besenmatter, Allan Svendsen, Jan H. Jensen
Format: Article
Language:English
Published: PeerJ Inc. 2013-08-01
Series:PeerJ
Subjects:
Enzyme Engineering
Computational Chemistry
Online Access:https://peerj.com/articles/145.pdf
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spelling doaj-9f0523c139a74fd5abf9b0e3f91f71b22020-11-24T22:38:59ZengPeerJ Inc.PeerJ2167-83592013-08-011e14510.7717/peerj.145145In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalBMartin R. Hediger0Luca De Vico1Julie B. Rannes2Christian Jäckel3Werner Besenmatter4Allan Svendsen5Jan H. Jensen6Department of Chemistry, University of Copenhagen, Copenhagen, DenmarkDepartment of Chemistry, University of Copenhagen, Copenhagen, DenmarkNovozymes A/S, Bagsværd, DenmarkNovozymes A/S, Bagsværd, DenmarkNovozymes A/S, Bagsværd, DenmarkNovozymes A/S, Bagsværd, DenmarkDepartment of Chemistry, University of Copenhagen, Copenhagen, DenmarkOur previously presented method for high throughput computational screening of mutant activity (Hediger et al., 2012) is benchmarked against experimentally measured amidase activity for 22 mutants of Candida antarctica lipase B (CalB). Using an appropriate cutoff criterion for the computed barriers, the qualitative activity of 15 out of 22 mutants is correctly predicted. The method identifies four of the six most active mutants with ≥3-fold wild type activity and seven out of the eight least active mutants with ≤0.5-fold wild type activity. The method is further used to screen all sterically possible (386) double-, triple- and quadruple-mutants constructed from the most active single mutants. Based on the benchmark test at least 20 new promising mutants are identified.https://peerj.com/articles/145.pdfEnzyme EngineeringComputational Chemistry
collection DOAJ
language English
format Article
sources DOAJ
author Martin R. Hediger
Luca De Vico
Julie B. Rannes
Christian Jäckel
Werner Besenmatter
Allan Svendsen
Jan H. Jensen
spellingShingle Martin R. Hediger
Luca De Vico
Julie B. Rannes
Christian Jäckel
Werner Besenmatter
Allan Svendsen
Jan H. Jensen
In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB
PeerJ
Enzyme Engineering
Computational Chemistry
author_facet Martin R. Hediger
Luca De Vico
Julie B. Rannes
Christian Jäckel
Werner Besenmatter
Allan Svendsen
Jan H. Jensen
author_sort Martin R. Hediger
title In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB
title_short In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB
title_full In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB
title_fullStr In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB
title_full_unstemmed In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB
title_sort in silico screening of 393 mutants facilitates enzyme engineering of amidase activity in calb
publisher PeerJ Inc.
series PeerJ
issn 2167-8359
publishDate 2013-08-01
description Our previously presented method for high throughput computational screening of mutant activity (Hediger et al., 2012) is benchmarked against experimentally measured amidase activity for 22 mutants of Candida antarctica lipase B (CalB). Using an appropriate cutoff criterion for the computed barriers, the qualitative activity of 15 out of 22 mutants is correctly predicted. The method identifies four of the six most active mutants with ≥3-fold wild type activity and seven out of the eight least active mutants with ≤0.5-fold wild type activity. The method is further used to screen all sterically possible (386) double-, triple- and quadruple-mutants constructed from the most active single mutants. Based on the benchmark test at least 20 new promising mutants are identified.
topic Enzyme Engineering
Computational Chemistry
url https://peerj.com/articles/145.pdf
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