Identification of New Drug Target in <i>Staphylococcus lugdunensis</i> by Subtractive Genomics Analysis and Their Inhibitors through Molecular Docking and Molecular Dynamic Simulation Studies
<i>Staphylococcus lugdunensis</i> is a coagulase-negative, Gram-positive, and human pathogenic bacteria. <i>S. lugdunensis</i> is the causative agent of diseases, such as native and prosthetic valve endocarditis, meningitis, septic arthritis, skin abscesses, brain abscess, br...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/9/9/451 |
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| author | Yahya Alhamhoom Umme Hani Fatima Ezzahra Bennani Noor Rahman Md Abdur Rashid Muhammad Naseer Abbas Luca Rastrelli |
| author_facet | Yahya Alhamhoom Umme Hani Fatima Ezzahra Bennani Noor Rahman Md Abdur Rashid Muhammad Naseer Abbas Luca Rastrelli |
| author_sort | Yahya Alhamhoom |
| collection | DOAJ |
| description | <i>Staphylococcus lugdunensis</i> is a coagulase-negative, Gram-positive, and human pathogenic bacteria. <i>S. lugdunensis</i> is the causative agent of diseases, such as native and prosthetic valve endocarditis, meningitis, septic arthritis, skin abscesses, brain abscess, breast abscesses, spondylodiscitis, post-surgical wound infections, bacteremia, and peritonitis. <i>S. lugdunensis</i> displays resistance to beta-lactam antibiotics due to the production of beta-lactamases. This study aimed to identify potential novel essential, human non-homologous, and non-gut flora drug targets in the <i>S. lugdunensis</i> strain N920143, and to evaluate the potential inhibitors of drug targets. The method was concerned with a homology search between the host and the pathogen proteome. Various tools, including the DEG (database of essential genes) for the essentiality of proteins, the KEGG for pathways analysis, CELLO V.2.5 for cellular localization prediction, and the drug bank database for predicting the druggability potential of proteins, were used. Furthermore, a similarity search with gut flora proteins was performed. A DNA-binding response-regulator protein was identified as a novel drug target against the N920143 strain of <i>S. lugdunensis</i>. The three-dimensional structure of the drug target was modelled and validated with the help of online tools. Furthermore, ten thousand drug-like compounds were retrieved from the ZINC15 database. The molecular docking approach for the DNA-binding response-regulator protein identified ZINC000020192004 and ZINC000020530348 as the most favorable compounds to interact with the active site residues of the drug target. These two compounds were subjected to an MD simulation study. Our analysis revealed that the identified compounds revealed more stable behavior when bound to the drug target DNA-binding response-regulator protein than the apostate. |
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| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-10T00:41:50Z |
| publishDate | 2022-09-01 |
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| series | Bioengineering |
| spelling | doaj.art-0e14f4331b4b4588ad1e216174e26d882023-11-23T15:05:49ZengMDPI AGBioengineering2306-53542022-09-019945110.3390/bioengineering9090451Identification of New Drug Target in <i>Staphylococcus lugdunensis</i> by Subtractive Genomics Analysis and Their Inhibitors through Molecular Docking and Molecular Dynamic Simulation StudiesYahya Alhamhoom0Umme Hani1Fatima Ezzahra Bennani2Noor Rahman3Md Abdur Rashid4Muhammad Naseer Abbas5Luca Rastrelli6Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi ArabiaLaboratory of Pharmacology and Toxicology, Bio Pharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and pharmacy, Mohammed V University in Rabat, BP6203 Rabat, MoroccoDepartment of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, PakistanDepartment of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi ArabiaDepartment of Pharmacy, Kohat University of Science and Technology (KUST), Kohat 26000, PakistanDipartimento di Farmacia, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy<i>Staphylococcus lugdunensis</i> is a coagulase-negative, Gram-positive, and human pathogenic bacteria. <i>S. lugdunensis</i> is the causative agent of diseases, such as native and prosthetic valve endocarditis, meningitis, septic arthritis, skin abscesses, brain abscess, breast abscesses, spondylodiscitis, post-surgical wound infections, bacteremia, and peritonitis. <i>S. lugdunensis</i> displays resistance to beta-lactam antibiotics due to the production of beta-lactamases. This study aimed to identify potential novel essential, human non-homologous, and non-gut flora drug targets in the <i>S. lugdunensis</i> strain N920143, and to evaluate the potential inhibitors of drug targets. The method was concerned with a homology search between the host and the pathogen proteome. Various tools, including the DEG (database of essential genes) for the essentiality of proteins, the KEGG for pathways analysis, CELLO V.2.5 for cellular localization prediction, and the drug bank database for predicting the druggability potential of proteins, were used. Furthermore, a similarity search with gut flora proteins was performed. A DNA-binding response-regulator protein was identified as a novel drug target against the N920143 strain of <i>S. lugdunensis</i>. The three-dimensional structure of the drug target was modelled and validated with the help of online tools. Furthermore, ten thousand drug-like compounds were retrieved from the ZINC15 database. The molecular docking approach for the DNA-binding response-regulator protein identified ZINC000020192004 and ZINC000020530348 as the most favorable compounds to interact with the active site residues of the drug target. These two compounds were subjected to an MD simulation study. Our analysis revealed that the identified compounds revealed more stable behavior when bound to the drug target DNA-binding response-regulator protein than the apostate.https://www.mdpi.com/2306-5354/9/9/451drug targetssubtractive genomicshomology modelingmolecular dockingmolecular dynamics simulation |
| spellingShingle | Yahya Alhamhoom Umme Hani Fatima Ezzahra Bennani Noor Rahman Md Abdur Rashid Muhammad Naseer Abbas Luca Rastrelli Identification of New Drug Target in <i>Staphylococcus lugdunensis</i> by Subtractive Genomics Analysis and Their Inhibitors through Molecular Docking and Molecular Dynamic Simulation Studies Bioengineering drug targets subtractive genomics homology modeling molecular docking molecular dynamics simulation |
| title | Identification of New Drug Target in <i>Staphylococcus lugdunensis</i> by Subtractive Genomics Analysis and Their Inhibitors through Molecular Docking and Molecular Dynamic Simulation Studies |
| title_full | Identification of New Drug Target in <i>Staphylococcus lugdunensis</i> by Subtractive Genomics Analysis and Their Inhibitors through Molecular Docking and Molecular Dynamic Simulation Studies |
| title_fullStr | Identification of New Drug Target in <i>Staphylococcus lugdunensis</i> by Subtractive Genomics Analysis and Their Inhibitors through Molecular Docking and Molecular Dynamic Simulation Studies |
| title_full_unstemmed | Identification of New Drug Target in <i>Staphylococcus lugdunensis</i> by Subtractive Genomics Analysis and Their Inhibitors through Molecular Docking and Molecular Dynamic Simulation Studies |
| title_short | Identification of New Drug Target in <i>Staphylococcus lugdunensis</i> by Subtractive Genomics Analysis and Their Inhibitors through Molecular Docking and Molecular Dynamic Simulation Studies |
| title_sort | identification of new drug target in i staphylococcus lugdunensis i by subtractive genomics analysis and their inhibitors through molecular docking and molecular dynamic simulation studies |
| topic | drug targets subtractive genomics homology modeling molecular docking molecular dynamics simulation |
| url | https://www.mdpi.com/2306-5354/9/9/451 |
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