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The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling

Zearalenone (ZEN) is one of the most prevalent estrogenic mycotoxins, is produced mainly by the Fusarium family of fungi, and poses a risk to the health of animals. Zearalenone hydrolase (ZHD) is an important enzyme capable of degrading ZEN into a non-toxic compound. Although previous research has i...

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Autores principales: Hong, Xi-Zhi, Han, Zheng-Gang, Yang, Jiang-Ke, Liu, Yi-Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254720/
https://www.ncbi.nlm.nih.gov/pubmed/37299021
http://dx.doi.org/10.3390/molecules28114545
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author Hong, Xi-Zhi
Han, Zheng-Gang
Yang, Jiang-Ke
Liu, Yi-Han
author_facet Hong, Xi-Zhi
Han, Zheng-Gang
Yang, Jiang-Ke
Liu, Yi-Han
author_sort Hong, Xi-Zhi
collection PubMed
description Zearalenone (ZEN) is one of the most prevalent estrogenic mycotoxins, is produced mainly by the Fusarium family of fungi, and poses a risk to the health of animals. Zearalenone hydrolase (ZHD) is an important enzyme capable of degrading ZEN into a non-toxic compound. Although previous research has investigated the catalytic mechanism of ZHD, information on its dynamic interaction with ZEN remains unknown. This study aimed to develop a pipeline for identifying the allosteric pathway of ZHD. Using an identity analysis, we identified hub genes whose sequences can generalize a set of sequences in a protein family. We then utilized a neural relational inference (NRI) model to identify the allosteric pathway of the protein throughout the entire molecular dynamics simulation. The production run lasted 1 microsecond, and we analyzed residues 139–222 for the allosteric pathway using the NRI model. We found that the cap domain of the protein opened up during catalysis, resembling a hemostatic tape. We used umbrella sampling to simulate the dynamic docking phase of the ligand–protein complex and found that the protein took on a square sandwich shape. Our energy analysis, using both molecular mechanics/Poisson–Boltzmann (Generalized-Born) surface area (MMPBSA) and Potential Mean Force (PMF) analysis, showed discrepancies, with scores of −8.45 kcal/mol and −1.95 kcal/mol, respectively. MMPBSA, however, obtained a similar score to that of a previous report.
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spelling pubmed-102547202023-06-10 The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling Hong, Xi-Zhi Han, Zheng-Gang Yang, Jiang-Ke Liu, Yi-Han Molecules Article Zearalenone (ZEN) is one of the most prevalent estrogenic mycotoxins, is produced mainly by the Fusarium family of fungi, and poses a risk to the health of animals. Zearalenone hydrolase (ZHD) is an important enzyme capable of degrading ZEN into a non-toxic compound. Although previous research has investigated the catalytic mechanism of ZHD, information on its dynamic interaction with ZEN remains unknown. This study aimed to develop a pipeline for identifying the allosteric pathway of ZHD. Using an identity analysis, we identified hub genes whose sequences can generalize a set of sequences in a protein family. We then utilized a neural relational inference (NRI) model to identify the allosteric pathway of the protein throughout the entire molecular dynamics simulation. The production run lasted 1 microsecond, and we analyzed residues 139–222 for the allosteric pathway using the NRI model. We found that the cap domain of the protein opened up during catalysis, resembling a hemostatic tape. We used umbrella sampling to simulate the dynamic docking phase of the ligand–protein complex and found that the protein took on a square sandwich shape. Our energy analysis, using both molecular mechanics/Poisson–Boltzmann (Generalized-Born) surface area (MMPBSA) and Potential Mean Force (PMF) analysis, showed discrepancies, with scores of −8.45 kcal/mol and −1.95 kcal/mol, respectively. MMPBSA, however, obtained a similar score to that of a previous report. MDPI 2023-06-04 /pmc/articles/PMC10254720/ /pubmed/37299021 http://dx.doi.org/10.3390/molecules28114545 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hong, Xi-Zhi
Han, Zheng-Gang
Yang, Jiang-Ke
Liu, Yi-Han
The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling
title The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling
title_full The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling
title_fullStr The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling
title_full_unstemmed The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling
title_short The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling
title_sort motion paradigm of pre-dock zearalenone hydrolase predictions with molecular dynamics and the docking phase with umbrella sampling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254720/
https://www.ncbi.nlm.nih.gov/pubmed/37299021
http://dx.doi.org/10.3390/molecules28114545
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