Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives
Biomolecular chemical simulations have recently become a useful research method in the fields of organic chemistry and bioscience. In the last few years, we have been focusing on the biomolecular computational simulation on lipase enzyme and ligand complexes to predict the enantioselectivity and rea...
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crsagepubl:10.1177/1934578x221108572 2023-05-15T14:13:36+02:00 Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives Yagi, Yoichiro Kimura, Takatomo Kamezawa, Makoto 2022 http://dx.doi.org/10.1177/1934578x221108572 http://journals.sagepub.com/doi/pdf/10.1177/1934578X221108572 http://journals.sagepub.com/doi/full-xml/10.1177/1934578X221108572 en eng SAGE Publications https://creativecommons.org/licenses/by-nc/4.0/ CC-BY-NC Natural Product Communications volume 17, issue 6, page 1934578X2211085 ISSN 1934-578X 1555-9475 Complementary and alternative medicine Plant Science Drug Discovery Pharmacology General Medicine journal-article 2022 crsagepubl https://doi.org/10.1177/1934578x221108572 2022-07-03T16:07:40Z Biomolecular chemical simulations have recently become a useful research method in the fields of organic chemistry and bioscience. In the last few years, we have been focusing on the biomolecular computational simulation on lipase enzyme and ligand complexes to predict the enantioselectivity and reactivity of lipases toward non-natural organic compounds. In this paper, we describe the molecular simulations including molecular dynamics (MD) and fragment molecular orbital (FMO) calculations for the complexes of Candida antarctica lipase type A (CALA) and trifluoromethylazulene alcohol derivatives. From the MD calculations, we found that the fast-reacting enantiomer of esters with high enantioselectivity stays in the vicinity of the active site of CALA, while the slow-reacting enantiomer leaves the active site of CALA. On the other hand, both ( R)- and ( S)-enantiomers of ester with low ensntioselectivity were found to keep near to near the active site of CALA. Further, for the esters that do not react with lipase enzyme, we found that both ( R)- and ( S)-enantiomers move away from the active site of lipase enzyme. From the FMO calculations, we found that each fast-reacting enantiomer of esters with high enantioselectivity strongly interacts with certain particular amino acid residues in CALA containing Asp95, while both ( R)- and ( S)-enantiomers of ester with low enantioselectivity interact with same amino acid residues in CALA including Asp95. These results suggest that it is possible to predict not only the enantioselectivity but also the reactivity of CALA and to identify the amino acid residues important to the enzymatic reaction. Therefore, we consider that our computational simulations would be a useful method for predicting and understanding the reactivity and the enantioselectivity of lipase-catalyzed biotransformations. Article in Journal/Newspaper Antarc* Antarctica SAGE Publications (via Crossref) Natural Product Communications 17 6 1934578X2211085 |
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Open Polar |
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SAGE Publications (via Crossref) |
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English |
topic |
Complementary and alternative medicine Plant Science Drug Discovery Pharmacology General Medicine |
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Complementary and alternative medicine Plant Science Drug Discovery Pharmacology General Medicine Yagi, Yoichiro Kimura, Takatomo Kamezawa, Makoto Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives |
topic_facet |
Complementary and alternative medicine Plant Science Drug Discovery Pharmacology General Medicine |
description |
Biomolecular chemical simulations have recently become a useful research method in the fields of organic chemistry and bioscience. In the last few years, we have been focusing on the biomolecular computational simulation on lipase enzyme and ligand complexes to predict the enantioselectivity and reactivity of lipases toward non-natural organic compounds. In this paper, we describe the molecular simulations including molecular dynamics (MD) and fragment molecular orbital (FMO) calculations for the complexes of Candida antarctica lipase type A (CALA) and trifluoromethylazulene alcohol derivatives. From the MD calculations, we found that the fast-reacting enantiomer of esters with high enantioselectivity stays in the vicinity of the active site of CALA, while the slow-reacting enantiomer leaves the active site of CALA. On the other hand, both ( R)- and ( S)-enantiomers of ester with low ensntioselectivity were found to keep near to near the active site of CALA. Further, for the esters that do not react with lipase enzyme, we found that both ( R)- and ( S)-enantiomers move away from the active site of lipase enzyme. From the FMO calculations, we found that each fast-reacting enantiomer of esters with high enantioselectivity strongly interacts with certain particular amino acid residues in CALA containing Asp95, while both ( R)- and ( S)-enantiomers of ester with low enantioselectivity interact with same amino acid residues in CALA including Asp95. These results suggest that it is possible to predict not only the enantioselectivity but also the reactivity of CALA and to identify the amino acid residues important to the enzymatic reaction. Therefore, we consider that our computational simulations would be a useful method for predicting and understanding the reactivity and the enantioselectivity of lipase-catalyzed biotransformations. |
format |
Article in Journal/Newspaper |
author |
Yagi, Yoichiro Kimura, Takatomo Kamezawa, Makoto |
author_facet |
Yagi, Yoichiro Kimura, Takatomo Kamezawa, Makoto |
author_sort |
Yagi, Yoichiro |
title |
Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives |
title_short |
Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives |
title_full |
Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives |
title_fullStr |
Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives |
title_full_unstemmed |
Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives |
title_sort |
biomolecular chemical simulations on enantioselectivity and reactivity of lipase enzymes to azulene derivatives |
publisher |
SAGE Publications |
publishDate |
2022 |
url |
http://dx.doi.org/10.1177/1934578x221108572 http://journals.sagepub.com/doi/pdf/10.1177/1934578X221108572 http://journals.sagepub.com/doi/full-xml/10.1177/1934578X221108572 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Natural Product Communications volume 17, issue 6, page 1934578X2211085 ISSN 1934-578X 1555-9475 |
op_rights |
https://creativecommons.org/licenses/by-nc/4.0/ |
op_rightsnorm |
CC-BY-NC |
op_doi |
https://doi.org/10.1177/1934578x221108572 |
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Natural Product Communications |
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17 |
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6 |
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1934578X2211085 |
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1766286046166777856 |