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 <span style=...

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Autores principales:	Xiaoqi Zheng, Tongyu Zheng, Yinglin Liao, Lianxiang Luo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>S. aureus</i> MurD enzyme virtual screening homology modelling ADME molecular dynamics Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/879fa55163224e98a6787058edea9253
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id	oai:doaj.org-article:879fa55163224e98a6787058edea9253
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spelling	oai:doaj.org-article:879fa55163224e98a6787058edea92532021-11-11T18:26:38ZIdentification of Potential Inhibitors of MurD Enzyme of <i>Staphylococcus aureus</i> from a Marine Natural Product Library10.3390/molecules262164261420-3049https://doaj.org/article/879fa55163224e98a6787058edea92532021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6426https://doaj.org/toc/1420-3049<i>Staphylococcus aureus</i> is an opportunistic pathogen that can cause fatal bacterial infections. MurD catalyzes the formation of peptide bond between UDP-<i>N</i>-acetylehyl-<span style="font-variant: small-caps;">l</span>-alanine and <span style="font-variant: small-caps;">d</span>-glutamic acid, which plays an important role in the synthesis of peptidoglycan and the formation of cell wall by <i>S. aureus</i>. Because <i>S. aureus</i> 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 <i>S. aureus</i>. 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 <i>S. aureus</i>. Through virtual screening, similarity screening, ADME study and molecular dynamics simulation, 46604 and 46608 were selected as potential drug candidates for <i>S. aureus</i>.Xiaoqi ZhengTongyu ZhengYinglin LiaoLianxiang LuoMDPI AGarticle<i>S. aureus</i> MurD enzymevirtual screeninghomology modellingADMEmolecular dynamicsOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6426, p 6426 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>S. aureus</i> MurD enzyme virtual screening homology modelling ADME molecular dynamics Organic chemistry QD241-441
spellingShingle	<i>S. aureus</i> MurD enzyme virtual screening homology modelling ADME molecular dynamics Organic chemistry QD241-441 Xiaoqi Zheng Tongyu Zheng Yinglin Liao Lianxiang Luo Identification of Potential Inhibitors of MurD Enzyme of <i>Staphylococcus aureus</i> from a Marine Natural Product Library
description	<i>Staphylococcus aureus</i> is an opportunistic pathogen that can cause fatal bacterial infections. MurD catalyzes the formation of peptide bond between UDP-<i>N</i>-acetylehyl-<span style="font-variant: small-caps;">l</span>-alanine and <span style="font-variant: small-caps;">d</span>-glutamic acid, which plays an important role in the synthesis of peptidoglycan and the formation of cell wall by <i>S. aureus</i>. Because <i>S. aureus</i> 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 <i>S. aureus</i>. 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 <i>S. aureus</i>. Through virtual screening, similarity screening, ADME study and molecular dynamics simulation, 46604 and 46608 were selected as potential drug candidates for <i>S. aureus</i>.
format	article
author	Xiaoqi Zheng Tongyu Zheng Yinglin Liao Lianxiang Luo
author_facet	Xiaoqi Zheng Tongyu Zheng Yinglin Liao Lianxiang Luo
author_sort	Xiaoqi Zheng
title	Identification of Potential Inhibitors of MurD Enzyme of <i>Staphylococcus aureus</i> from a Marine Natural Product Library
title_short	Identification of Potential Inhibitors of MurD Enzyme of <i>Staphylococcus aureus</i> from a Marine Natural Product Library
title_full	Identification of Potential Inhibitors of MurD Enzyme of <i>Staphylococcus aureus</i> from a Marine Natural Product Library
title_fullStr	Identification of Potential Inhibitors of MurD Enzyme of <i>Staphylococcus aureus</i> from a Marine Natural Product Library
title_full_unstemmed	Identification of Potential Inhibitors of MurD Enzyme of <i>Staphylococcus aureus</i> from a Marine Natural Product Library
title_sort	identification of potential inhibitors of murd enzyme of <i>staphylococcus aureus</i> from a marine natural product library
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/879fa55163224e98a6787058edea9253
work_keys_str_mv	AT xiaoqizheng identificationofpotentialinhibitorsofmurdenzymeofistaphylococcusaureusifromamarinenaturalproductlibrary AT tongyuzheng identificationofpotentialinhibitorsofmurdenzymeofistaphylococcusaureusifromamarinenaturalproductlibrary AT yinglinliao identificationofpotentialinhibitorsofmurdenzymeofistaphylococcusaureusifromamarinenaturalproductlibrary AT lianxiangluo identificationofpotentialinhibitorsofmurdenzymeofistaphylococcusaureusifromamarinenaturalproductlibrary
_version_	1718431834638909440

Identification of Potential Inhibitors of MurD Enzyme of <i>Staphylococcus aureus</i> from a Marine Natural Product Library

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