Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study
Abstract A major problem in predicting the enantioselectivity of an enzyme toward substrate molecules is that even high selectivity toward one substrate enantiomer over the other corresponds to a very small difference in free energy. However, total free energies in enzyme‐substrate systems are very...
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crwiley:10.1110/ps.33901 2024-06-23T07:46:17+00:00 Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study Raza, Sami Fransson, Linda Hult, Karl 2001 http://dx.doi.org/10.1110/ps.33901 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1110%2Fps.33901 https://onlinelibrary.wiley.com/doi/pdf/10.1110/ps.33901 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Protein Science volume 10, issue 2, page 329-338 ISSN 0961-8368 1469-896X journal-article 2001 crwiley https://doi.org/10.1110/ps.33901 2024-06-13T04:21:34Z Abstract A major problem in predicting the enantioselectivity of an enzyme toward substrate molecules is that even high selectivity toward one substrate enantiomer over the other corresponds to a very small difference in free energy. However, total free energies in enzyme‐substrate systems are very large and fluctuate significantly because of general protein motion. Candida antarctica lipase B (CALB), a serine hydrolase, displays enantioselectivity toward secondary alcohols. Here, we present a modeling study where the aim has been to develop a molecular dynamics‐based methodology for the prediction of enantioselectivity in CALB. The substrates modeled (seven in total) were 3‐methyl‐2‐butanol with various aliphatic carboxylic acids and also 2‐butanol, as well as 3,3‐dimethyl‐2‐butanol with octanoic acid. The tetrahedral reaction intermediate was used as a model of the transition state. Investigative analyses were performed on ensembles of nonminimized structures and focused on the potential energies of a number of subsets within the modeled systems to determine which specific regions are important for the prediction of enantioselectivity. One category of subset was based on atoms that make up the core structural elements of the transition state. We considered that a more favorable energetic conformation of such a subset should relate to a greater likelihood for catalysis to occur, thus reflecting higher selectivity. The results of this study conveyed that the use of this type of subset was viable for the analysis of structural ensembles and yielded good predictions of enantioselectivity. Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library Protein Science 10 2 329 338 |
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English |
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Abstract A major problem in predicting the enantioselectivity of an enzyme toward substrate molecules is that even high selectivity toward one substrate enantiomer over the other corresponds to a very small difference in free energy. However, total free energies in enzyme‐substrate systems are very large and fluctuate significantly because of general protein motion. Candida antarctica lipase B (CALB), a serine hydrolase, displays enantioselectivity toward secondary alcohols. Here, we present a modeling study where the aim has been to develop a molecular dynamics‐based methodology for the prediction of enantioselectivity in CALB. The substrates modeled (seven in total) were 3‐methyl‐2‐butanol with various aliphatic carboxylic acids and also 2‐butanol, as well as 3,3‐dimethyl‐2‐butanol with octanoic acid. The tetrahedral reaction intermediate was used as a model of the transition state. Investigative analyses were performed on ensembles of nonminimized structures and focused on the potential energies of a number of subsets within the modeled systems to determine which specific regions are important for the prediction of enantioselectivity. One category of subset was based on atoms that make up the core structural elements of the transition state. We considered that a more favorable energetic conformation of such a subset should relate to a greater likelihood for catalysis to occur, thus reflecting higher selectivity. The results of this study conveyed that the use of this type of subset was viable for the analysis of structural ensembles and yielded good predictions of enantioselectivity. |
format |
Article in Journal/Newspaper |
author |
Raza, Sami Fransson, Linda Hult, Karl |
spellingShingle |
Raza, Sami Fransson, Linda Hult, Karl Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study |
author_facet |
Raza, Sami Fransson, Linda Hult, Karl |
author_sort |
Raza, Sami |
title |
Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study |
title_short |
Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study |
title_full |
Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study |
title_fullStr |
Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study |
title_full_unstemmed |
Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study |
title_sort |
enantioselectivity in candida antarctica lipase b: a molecular dynamics study |
publisher |
Wiley |
publishDate |
2001 |
url |
http://dx.doi.org/10.1110/ps.33901 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1110%2Fps.33901 https://onlinelibrary.wiley.com/doi/pdf/10.1110/ps.33901 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Protein Science volume 10, issue 2, page 329-338 ISSN 0961-8368 1469-896X |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1110/ps.33901 |
container_title |
Protein Science |
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10 |
container_issue |
2 |
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329 |
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338 |
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1802645021954932736 |