Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B
ABSTRACT The prospect for computer‐aided refinement of stereoselective enzymes is further validated by simulating the ester hydrolysis by the wild‐type and mutants of CalB, focusing on the challenge of dealing with strong steric effects and entropic contributions. This was done using the empirical v...
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crwiley:10.1002/prot.24506 2024-09-30T14:26:13+00:00 Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B Schopf, Patrick Warshel, Arieh 2014 http://dx.doi.org/10.1002/prot.24506 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fprot.24506 https://onlinelibrary.wiley.com/doi/pdf/10.1002/prot.24506 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Proteins: Structure, Function, and Bioinformatics volume 82, issue 7, page 1387-1399 ISSN 0887-3585 1097-0134 journal-article 2014 crwiley https://doi.org/10.1002/prot.24506 2024-09-17T04:45:22Z ABSTRACT The prospect for computer‐aided refinement of stereoselective enzymes is further validated by simulating the ester hydrolysis by the wild‐type and mutants of CalB, focusing on the challenge of dealing with strong steric effects and entropic contributions. This was done using the empirical valence bond (EVB) method in a quantitative screening of the enantioselectivity, considering both k cat and k cat / K M of the R and S stereoisomers. Although the simulations require very extensive sampling for convergence they give encouraging results and major validation, indicating that our approach offers a powerful tool for computer‐aided design of enantioselective enzymes. This is particularly true in cases with large changes in steric effects where alternative approaches may have difficulties in capturing the interplay between steric clashes with the reacting substrate and protein flexibility. Proteins 2014; 82:1387–1399. © 2014 Wiley Periodicals, Inc. Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library Proteins: Structure, Function, and Bioinformatics 82 7 1387 1399 |
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Wiley Online Library |
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English |
description |
ABSTRACT The prospect for computer‐aided refinement of stereoselective enzymes is further validated by simulating the ester hydrolysis by the wild‐type and mutants of CalB, focusing on the challenge of dealing with strong steric effects and entropic contributions. This was done using the empirical valence bond (EVB) method in a quantitative screening of the enantioselectivity, considering both k cat and k cat / K M of the R and S stereoisomers. Although the simulations require very extensive sampling for convergence they give encouraging results and major validation, indicating that our approach offers a powerful tool for computer‐aided design of enantioselective enzymes. This is particularly true in cases with large changes in steric effects where alternative approaches may have difficulties in capturing the interplay between steric clashes with the reacting substrate and protein flexibility. Proteins 2014; 82:1387–1399. © 2014 Wiley Periodicals, Inc. |
format |
Article in Journal/Newspaper |
author |
Schopf, Patrick Warshel, Arieh |
spellingShingle |
Schopf, Patrick Warshel, Arieh Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B |
author_facet |
Schopf, Patrick Warshel, Arieh |
author_sort |
Schopf, Patrick |
title |
Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B |
title_short |
Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B |
title_full |
Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B |
title_fullStr |
Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B |
title_full_unstemmed |
Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B |
title_sort |
validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in candida antarctica lipase b |
publisher |
Wiley |
publishDate |
2014 |
url |
http://dx.doi.org/10.1002/prot.24506 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fprot.24506 https://onlinelibrary.wiley.com/doi/pdf/10.1002/prot.24506 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Proteins: Structure, Function, and Bioinformatics volume 82, issue 7, page 1387-1399 ISSN 0887-3585 1097-0134 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/prot.24506 |
container_title |
Proteins: Structure, Function, and Bioinformatics |
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82 |
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7 |
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1387 |
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1399 |
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1811646653886627840 |