In silico discovery of druggable targets in Citrobacter koseri using echinoderm metabolites and molecular dynamics simulation
Abstract Citrobacter koseri causes infection in people who are immunocompromised. Without effective antibiotics, these infections can become severe and life-threatening, so effective drugs are essential to treat these infections. Utilizing subtractive genomics, 2699 ORFs were predicted and translate...
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-77342-5 |
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| author | Bayan A. Alhaidhal Fatimah M. Alsulais Ramzi A. Mothana Abdullah R. Alanzi |
| author_facet | Bayan A. Alhaidhal Fatimah M. Alsulais Ramzi A. Mothana Abdullah R. Alanzi |
| author_sort | Bayan A. Alhaidhal |
| collection | DOAJ |
| description | Abstract Citrobacter koseri causes infection in people who are immunocompromised. Without effective antibiotics, these infections can become severe and life-threatening, so effective drugs are essential to treat these infections. Utilizing subtractive genomics, 2699 ORFs were predicted and translated into amino acid sequences. Metabolic pathway analysis and subcellular localization helped define the roles of key bacterial proteins. Two druggable proteins, WP_012000829.1 and WP_275157394.1, were discovered as promising targets. Alpha Fold provided 3D structures, and a library of 1600 echinoderm metabolites was docked against these proteins, with Ampicillin, Levofloxacin, and Doxycycline as controls. Notably, CMNPD13085 and CMNPD15632 exhibited the highest binding affinities for WP_012000829.1 and WP_275157394.1, respectively. Molecular dynamics simulations and MM-GBSA binding free energy complemented docking results. However, acknowledging the reliance on computational validations, the study emphasizes the need for essential in-vitro research to transform these potential inhibitors into therapeutic drugs. |
| format | Article |
| id | doaj-art-6f12c089c9d743dd97cdba04bb59fede |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-6f12c089c9d743dd97cdba04bb59fede2025-08-20T02:49:57ZengNature PortfolioScientific Reports2045-23222024-11-0114111510.1038/s41598-024-77342-5In silico discovery of druggable targets in Citrobacter koseri using echinoderm metabolites and molecular dynamics simulationBayan A. Alhaidhal0Fatimah M. Alsulais1Ramzi A. Mothana2Abdullah R. Alanzi3Department of Pharmacognosy, College of Pharmacy, King Saud UniversityDepartment of Pharmacognosy, College of Pharmacy, King Saud UniversityDepartment of Pharmacognosy, College of Pharmacy, King Saud UniversityDepartment of Pharmacognosy, College of Pharmacy, King Saud UniversityAbstract Citrobacter koseri causes infection in people who are immunocompromised. Without effective antibiotics, these infections can become severe and life-threatening, so effective drugs are essential to treat these infections. Utilizing subtractive genomics, 2699 ORFs were predicted and translated into amino acid sequences. Metabolic pathway analysis and subcellular localization helped define the roles of key bacterial proteins. Two druggable proteins, WP_012000829.1 and WP_275157394.1, were discovered as promising targets. Alpha Fold provided 3D structures, and a library of 1600 echinoderm metabolites was docked against these proteins, with Ampicillin, Levofloxacin, and Doxycycline as controls. Notably, CMNPD13085 and CMNPD15632 exhibited the highest binding affinities for WP_012000829.1 and WP_275157394.1, respectively. Molecular dynamics simulations and MM-GBSA binding free energy complemented docking results. However, acknowledging the reliance on computational validations, the study emphasizes the need for essential in-vitro research to transform these potential inhibitors into therapeutic drugs.https://doi.org/10.1038/s41598-024-77342-5Citrobacter koseriImmunocompromisedSubtractive genomicsMolecular dockingMD simulationMMGBSA |
| spellingShingle | Bayan A. Alhaidhal Fatimah M. Alsulais Ramzi A. Mothana Abdullah R. Alanzi In silico discovery of druggable targets in Citrobacter koseri using echinoderm metabolites and molecular dynamics simulation Scientific Reports Citrobacter koseri Immunocompromised Subtractive genomics Molecular docking MD simulation MMGBSA |
| title | In silico discovery of druggable targets in Citrobacter koseri using echinoderm metabolites and molecular dynamics simulation |
| title_full | In silico discovery of druggable targets in Citrobacter koseri using echinoderm metabolites and molecular dynamics simulation |
| title_fullStr | In silico discovery of druggable targets in Citrobacter koseri using echinoderm metabolites and molecular dynamics simulation |
| title_full_unstemmed | In silico discovery of druggable targets in Citrobacter koseri using echinoderm metabolites and molecular dynamics simulation |
| title_short | In silico discovery of druggable targets in Citrobacter koseri using echinoderm metabolites and molecular dynamics simulation |
| title_sort | in silico discovery of druggable targets in citrobacter koseri using echinoderm metabolites and molecular dynamics simulation |
| topic | Citrobacter koseri Immunocompromised Subtractive genomics Molecular docking MD simulation MMGBSA |
| url | https://doi.org/10.1038/s41598-024-77342-5 |
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