Identification of Potential Inhibitors of MurD Enzyme of <i>Staphylococcus aureus</i> from a Marine Natural Product Library
<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=...
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| Autores principales: | , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/879fa55163224e98a6787058edea9253 |
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| Sumario: | <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>. |
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