The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling
-
Published:2023-06-04
Issue:11
Volume:28
Page:4545
-
ISSN:1420-3049
-
Container-title:Molecules
-
language:en
-
Short-container-title:Molecules
Author:
Hong Xi-Zhi1, Han Zheng-Gang1, Yang Jiang-Ke1, Liu Yi-Han2ORCID
Affiliation:
1. Pilot Base of Food Microbial Resources Utilization of Hubei Province, College of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, China 2. Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300453, China
Abstract
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.
Funder
National Key Research and Development Program of China Key R&D projects in Hubei Province, China
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference26 articles.
1. Mycotoxins;Bennett;Clin. Microbiol. Rev.,2003 2. Degradation of zearalenone in swine feed and feed ingredients by Bacillus subtilis ANSB01G;Lei;World Mycotoxin J.,2014 3. Gruber-Dorninger, C., Jenkins, T., and Schatzmayr, G. (2019). Global Mycotoxin Occurrence in Feed: A Ten-Year Survey. Toxins, 11. 4. Stability of mycotoxins during food processing;Bullerman;Int. J. Food Microbiol.,2007 5. Yang, K., Li, K., Pan, L., Luo, X., Xing, J., Wang, J., Wang, L., Wang, R., Zhai, Y., and Chen, Z. (2002). Effect of Ozone and Electron Beam Irradiation on Degradation of Zearalenone and Ochratoxin A. Toxins, 12.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|