New drug target identification in Vibrio vulnificus by subtractive genome analysis and their inhibitors through molecular docking and molecular dynamics simulations
Vibrio vulnificus is a rod shape, Gram-negative bacterium that causes sepsis (with a greater than 50% mortality rate), necrotizing fasciitis, gastroenteritis, skin, and soft tissue infection, wound infection, peritonitis, meningitis, pneumonia, keratitis, and arthritis. Based on pathogenicity V. vul...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023048582 |
| _version_ | 1827892333350223872 |
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| author | Bader S. Alotaibi Amar Ajmal Mohammed Ageeli Hakami Arif Mahmood Abdul Wadood Junjian Hu |
| author_facet | Bader S. Alotaibi Amar Ajmal Mohammed Ageeli Hakami Arif Mahmood Abdul Wadood Junjian Hu |
| author_sort | Bader S. Alotaibi |
| collection | DOAJ |
| description | Vibrio vulnificus is a rod shape, Gram-negative bacterium that causes sepsis (with a greater than 50% mortality rate), necrotizing fasciitis, gastroenteritis, skin, and soft tissue infection, wound infection, peritonitis, meningitis, pneumonia, keratitis, and arthritis. Based on pathogenicity V. vulnificus is categorized into three biotypes. Type 1 and type 3 cause diseases in humans while biotype 2 causes diseases in eel and fish. Due to indiscriminate use of antibiotics V. vulnificus has developed resistance to many antibiotics so curing is dramatically a challenge. V. vulnificus is resistant to cefazolin, streptomycin, tetracycline, aztreonam, tobramycin, cefepime, and gentamycin. Subtractive genome analysis is the most effective method for drug target identification. The method is based on the subtraction of homologous proteins from both pathogen and host. By this process set of proteins present only in the pathogen and perform essential functions in the pathogen can be identified. The entire proteome of Vibrio vulnificus strain ATCC 27562 was reduced step by step to a single protein predicted as the drug target. AlphaFold2 is one of the applications of deep learning algorithms in biomedicine and is correctly considered the game changer in the field of structural biology. Accuracy and speed are the major strength of AlphaFold2. In the PDB database, the crystal structure of the predicted drug target was not present, therefore the Colab notebook was used to predict the 3D structure by the AlphaFold2, and subsequently, the predicted model was validated. Potent inhibitors against the new target were predicted by virtual screening and molecular docking study. The most stable compound ZINC01318774 tightly attaches to the binding pocket of bisphosphoglycerate-independent phosphoglycerate mutase. The time-dependent molecular dynamics simulation revealed compound ZINC01318774 was superior as compared to the standard drug tetracycline in terms of stability. The availability of V. vulnificus strain ATCC 27562 has allowed in silico identification of drug target which will provide a base for the discovery of specific therapeutic targets against Vibrio vulnificus. |
| first_indexed | 2024-03-12T21:38:16Z |
| format | Article |
| id | doaj.art-39bbacaf7adb4c82967d0203e57f5c3b |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-12T21:38:16Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-39bbacaf7adb4c82967d0203e57f5c3b2023-07-27T05:56:56ZengElsevierHeliyon2405-84402023-07-0197e17650New drug target identification in Vibrio vulnificus by subtractive genome analysis and their inhibitors through molecular docking and molecular dynamics simulationsBader S. Alotaibi0Amar Ajmal1Mohammed Ageeli Hakami2Arif Mahmood3Abdul Wadood4Junjian Hu5Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al-Quwayiyah, Shaqra Univesity, Riyadh, Saudi ArabiaDepartment of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan, PakistanDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al-Quwayiyah, Shaqra Univesity, Riyadh, Saudi ArabiaCenter for Medical Genetics and Human Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, Hunan, ChinaDepartment of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan, Pakistan; Corresponding author.Department of Central Laboratory, SSL, Central Hospital of Gongguan City, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, China; Corresponding author.Vibrio vulnificus is a rod shape, Gram-negative bacterium that causes sepsis (with a greater than 50% mortality rate), necrotizing fasciitis, gastroenteritis, skin, and soft tissue infection, wound infection, peritonitis, meningitis, pneumonia, keratitis, and arthritis. Based on pathogenicity V. vulnificus is categorized into three biotypes. Type 1 and type 3 cause diseases in humans while biotype 2 causes diseases in eel and fish. Due to indiscriminate use of antibiotics V. vulnificus has developed resistance to many antibiotics so curing is dramatically a challenge. V. vulnificus is resistant to cefazolin, streptomycin, tetracycline, aztreonam, tobramycin, cefepime, and gentamycin. Subtractive genome analysis is the most effective method for drug target identification. The method is based on the subtraction of homologous proteins from both pathogen and host. By this process set of proteins present only in the pathogen and perform essential functions in the pathogen can be identified. The entire proteome of Vibrio vulnificus strain ATCC 27562 was reduced step by step to a single protein predicted as the drug target. AlphaFold2 is one of the applications of deep learning algorithms in biomedicine and is correctly considered the game changer in the field of structural biology. Accuracy and speed are the major strength of AlphaFold2. In the PDB database, the crystal structure of the predicted drug target was not present, therefore the Colab notebook was used to predict the 3D structure by the AlphaFold2, and subsequently, the predicted model was validated. Potent inhibitors against the new target were predicted by virtual screening and molecular docking study. The most stable compound ZINC01318774 tightly attaches to the binding pocket of bisphosphoglycerate-independent phosphoglycerate mutase. The time-dependent molecular dynamics simulation revealed compound ZINC01318774 was superior as compared to the standard drug tetracycline in terms of stability. The availability of V. vulnificus strain ATCC 27562 has allowed in silico identification of drug target which will provide a base for the discovery of specific therapeutic targets against Vibrio vulnificus.http://www.sciencedirect.com/science/article/pii/S2405844023048582Vibrio vulnificusSubtractive genomicsNew drug targetAlphafold2MD simulation |
| spellingShingle | Bader S. Alotaibi Amar Ajmal Mohammed Ageeli Hakami Arif Mahmood Abdul Wadood Junjian Hu New drug target identification in Vibrio vulnificus by subtractive genome analysis and their inhibitors through molecular docking and molecular dynamics simulations Heliyon Vibrio vulnificus Subtractive genomics New drug target Alphafold2 MD simulation |
| title | New drug target identification in Vibrio vulnificus by subtractive genome analysis and their inhibitors through molecular docking and molecular dynamics simulations |
| title_full | New drug target identification in Vibrio vulnificus by subtractive genome analysis and their inhibitors through molecular docking and molecular dynamics simulations |
| title_fullStr | New drug target identification in Vibrio vulnificus by subtractive genome analysis and their inhibitors through molecular docking and molecular dynamics simulations |
| title_full_unstemmed | New drug target identification in Vibrio vulnificus by subtractive genome analysis and their inhibitors through molecular docking and molecular dynamics simulations |
| title_short | New drug target identification in Vibrio vulnificus by subtractive genome analysis and their inhibitors through molecular docking and molecular dynamics simulations |
| title_sort | new drug target identification in vibrio vulnificus by subtractive genome analysis and their inhibitors through molecular docking and molecular dynamics simulations |
| topic | Vibrio vulnificus Subtractive genomics New drug target Alphafold2 MD simulation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023048582 |
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