Towards Quantitative Computer‐Aided Studies of Enzymatic Enantioselectivity: The Case of Candida antarctica Lipase A
Abstract The prospect for consistent computer‐aided refinement of stereoselective enzymes is explored by simulating the hydrolysis of enantiomers of an α‐substituted ester by wild‐type and mutant Candida antarctica lipase A, using several strategies. In particular, we focused on the use of the empir...
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crwiley:10.1002/cbic.201100600 2024-06-23T07:47:16+00:00 Towards Quantitative Computer‐Aided Studies of Enzymatic Enantioselectivity: The Case of Candida antarctica Lipase A Frushicheva, Maria P. Warshel, Arieh 2011 http://dx.doi.org/10.1002/cbic.201100600 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcbic.201100600 https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201100600 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor ChemBioChem volume 13, issue 2, page 215-223 ISSN 1439-4227 1439-7633 journal-article 2011 crwiley https://doi.org/10.1002/cbic.201100600 2024-06-04T06:47:42Z Abstract The prospect for consistent computer‐aided refinement of stereoselective enzymes is explored by simulating the hydrolysis of enantiomers of an α‐substituted ester by wild‐type and mutant Candida antarctica lipase A, using several strategies. In particular, we focused on the use of the empirical valence bond (EVB) method in a quantitative screening for enantioselectivity, and evaluate both k cat and k cat / K M of the R and S stereoisomers. We found that an extensive sampling is essential for obtaining converging results. This requirement points towards possible problems with approaches that use a limited conformational sampling. However, performing the proper sampling appears to give encouraging results and to offer a powerful tool for the computer‐aided design of enantioselective enzymes. We also explore faster strategies for identifying mutations that will help in augmenting directed‐evolution experiments, but these approaches require further refinement. Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library ChemBioChem 13 2 215 223 |
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English |
description |
Abstract The prospect for consistent computer‐aided refinement of stereoselective enzymes is explored by simulating the hydrolysis of enantiomers of an α‐substituted ester by wild‐type and mutant Candida antarctica lipase A, using several strategies. In particular, we focused on the use of the empirical valence bond (EVB) method in a quantitative screening for enantioselectivity, and evaluate both k cat and k cat / K M of the R and S stereoisomers. We found that an extensive sampling is essential for obtaining converging results. This requirement points towards possible problems with approaches that use a limited conformational sampling. However, performing the proper sampling appears to give encouraging results and to offer a powerful tool for the computer‐aided design of enantioselective enzymes. We also explore faster strategies for identifying mutations that will help in augmenting directed‐evolution experiments, but these approaches require further refinement. |
format |
Article in Journal/Newspaper |
author |
Frushicheva, Maria P. Warshel, Arieh |
spellingShingle |
Frushicheva, Maria P. Warshel, Arieh Towards Quantitative Computer‐Aided Studies of Enzymatic Enantioselectivity: The Case of Candida antarctica Lipase A |
author_facet |
Frushicheva, Maria P. Warshel, Arieh |
author_sort |
Frushicheva, Maria P. |
title |
Towards Quantitative Computer‐Aided Studies of Enzymatic Enantioselectivity: The Case of Candida antarctica Lipase A |
title_short |
Towards Quantitative Computer‐Aided Studies of Enzymatic Enantioselectivity: The Case of Candida antarctica Lipase A |
title_full |
Towards Quantitative Computer‐Aided Studies of Enzymatic Enantioselectivity: The Case of Candida antarctica Lipase A |
title_fullStr |
Towards Quantitative Computer‐Aided Studies of Enzymatic Enantioselectivity: The Case of Candida antarctica Lipase A |
title_full_unstemmed |
Towards Quantitative Computer‐Aided Studies of Enzymatic Enantioselectivity: The Case of Candida antarctica Lipase A |
title_sort |
towards quantitative computer‐aided studies of enzymatic enantioselectivity: the case of candida antarctica lipase a |
publisher |
Wiley |
publishDate |
2011 |
url |
http://dx.doi.org/10.1002/cbic.201100600 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcbic.201100600 https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201100600 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
ChemBioChem volume 13, issue 2, page 215-223 ISSN 1439-4227 1439-7633 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/cbic.201100600 |
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ChemBioChem |
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13 |
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2 |
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215 |
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223 |
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1802651365330124800 |