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Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library

Staphylococcus aureus is an opportunistic pathogen that can cause fatal bacterial infections. MurD catalyzes the formation of peptide bond between UDP-N-acetylehyl-l-alanine and d-glutamic acid, which plays an important role in the synthesis of peptidoglycan and the formation of cell wall by S. aure...

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Autores principales: Zheng, Xiaoqi, Zheng, Tongyu, Liao, Yinglin, Luo, Lianxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587310/
https://www.ncbi.nlm.nih.gov/pubmed/34770835
http://dx.doi.org/10.3390/molecules26216426
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author Zheng, Xiaoqi
Zheng, Tongyu
Liao, Yinglin
Luo, Lianxiang
author_facet Zheng, Xiaoqi
Zheng, Tongyu
Liao, Yinglin
Luo, Lianxiang
author_sort Zheng, Xiaoqi
collection PubMed
description Staphylococcus aureus is an opportunistic pathogen that can cause fatal bacterial infections. MurD catalyzes the formation of peptide bond between UDP-N-acetylehyl-l-alanine and d-glutamic acid, which plays an important role in the synthesis of peptidoglycan and the formation of cell wall by S. aureus. Because S. aureus is resistant to most existing antibiotics, it is necessary to develop new inhibitors. In this study, Schrodinger 11.5 Prime homology modeling was selected to prepare the protein model of MurD enzyme, and its structure was optimized. We used a virtual screening program and similarity screening to screen 47163 compounds from three marine natural product libraries to explore new inhibitors of S. aureus. ADME provides analysis of the physicochemical properties of the best performing compounds during the screening process. To determine the stability of the docking effect, a 100 ns molecular dynamics was performed to verify how tightly the compound was bound to the protein. By docking analysis and molecular dynamics analysis, both 46604 and 46608 have strong interaction with the docking pocket, have good pharmacological properties, and maintain stable conformation with the target protein, so they have a chance to become drugs for S. aureus. Through virtual screening, similarity screening, ADME study and molecular dynamics simulation, 46604 and 46608 were selected as potential drug candidates for S. aureus.
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spelling pubmed-85873102021-11-13 Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library Zheng, Xiaoqi Zheng, Tongyu Liao, Yinglin Luo, Lianxiang Molecules Article Staphylococcus aureus is an opportunistic pathogen that can cause fatal bacterial infections. MurD catalyzes the formation of peptide bond between UDP-N-acetylehyl-l-alanine and d-glutamic acid, which plays an important role in the synthesis of peptidoglycan and the formation of cell wall by S. aureus. Because S. aureus is resistant to most existing antibiotics, it is necessary to develop new inhibitors. In this study, Schrodinger 11.5 Prime homology modeling was selected to prepare the protein model of MurD enzyme, and its structure was optimized. We used a virtual screening program and similarity screening to screen 47163 compounds from three marine natural product libraries to explore new inhibitors of S. aureus. ADME provides analysis of the physicochemical properties of the best performing compounds during the screening process. To determine the stability of the docking effect, a 100 ns molecular dynamics was performed to verify how tightly the compound was bound to the protein. By docking analysis and molecular dynamics analysis, both 46604 and 46608 have strong interaction with the docking pocket, have good pharmacological properties, and maintain stable conformation with the target protein, so they have a chance to become drugs for S. aureus. Through virtual screening, similarity screening, ADME study and molecular dynamics simulation, 46604 and 46608 were selected as potential drug candidates for S. aureus. MDPI 2021-10-25 /pmc/articles/PMC8587310/ /pubmed/34770835 http://dx.doi.org/10.3390/molecules26216426 Text en © 2021 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
Zheng, Xiaoqi
Zheng, Tongyu
Liao, Yinglin
Luo, Lianxiang
Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library
title Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library
title_full Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library
title_fullStr Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library
title_full_unstemmed Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library
title_short Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library
title_sort identification of potential inhibitors of murd enzyme of staphylococcus aureus from a marine natural product library
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587310/
https://www.ncbi.nlm.nih.gov/pubmed/34770835
http://dx.doi.org/10.3390/molecules26216426
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