A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates
Prostate cancer is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa at 5.2% with the majority of diagnosed patients found to have advanced disease. This study aimed to use the STEAP2 protein (prostate...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Bioinformatics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbinf.2022.869375/full |
| _version_ | 1818212951765549056 |
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| author | Timothy Ongaba Christian Ndekezi Christian Ndekezi Nana Nakiddu Nana Nakiddu |
| author_facet | Timothy Ongaba Christian Ndekezi Christian Ndekezi Nana Nakiddu Nana Nakiddu |
| author_sort | Timothy Ongaba |
| collection | DOAJ |
| description | Prostate cancer is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa at 5.2% with the majority of diagnosed patients found to have advanced disease. This study aimed to use the STEAP2 protein (prostate cancer–specific biomarker) for the discovery of new targeted therapy. To determine the most likely compound that can bind to the STEAP2 protein, we docked the modeled STEAP2 3D structure against 2466 FDA (Food and Drug Administration)-approved drug candidates using AutoDock Vina. Protein basic local alignment search tool (BLASTp) search, multiple sequence alignment (MSA), and phylogenetics were further carried out to analyze the diversity of this marker and determine its conserved domains as suitable target regions. Six promising drug candidates (ligands) were identified. Triptorelin had the highest binding energy (−12.1 kcal/mol) followed by leuprolide (docking energy: −11.2 kcal/mol). All the top two drug candidates interacted with residues Ser-372 and Gly-369 in close proximity with the iron-binding domain (an important catalyst of metal reduction). The two drugs had earlier been approved for the treatment of advanced prostate cancer with an elusive mode of action. Through this study, further insight into figuring out their interaction with STEAP2 might be important during treatment. |
| first_indexed | 2024-12-12T05:56:33Z |
| format | Article |
| id | doaj.art-c66ae12599b34b05b101e44d193f32f4 |
| institution | Directory Open Access Journal |
| issn | 2673-7647 |
| language | English |
| last_indexed | 2024-12-12T05:56:33Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioinformatics |
| spelling | doaj.art-c66ae12599b34b05b101e44d193f32f42022-12-22T00:35:33ZengFrontiers Media S.A.Frontiers in Bioinformatics2673-76472022-05-01210.3389/fbinf.2022.869375869375A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic CandidatesTimothy Ongaba0Christian Ndekezi1Christian Ndekezi2Nana Nakiddu3Nana Nakiddu4Department of Biomolecular Resources and Biolaboratory Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity (CoVAB), Makerere University, Kampala, UgandaDepartment of Biomolecular Resources and Biolaboratory Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity (CoVAB), Makerere University, Kampala, UgandaUganda Virus Research Institute, Entebbe, UgandaJoint Clinical Research Centre, Kampala, UgandaCollege of Health Sciences (CHS), Makerere University, Kampala, UgandaProstate cancer is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa at 5.2% with the majority of diagnosed patients found to have advanced disease. This study aimed to use the STEAP2 protein (prostate cancer–specific biomarker) for the discovery of new targeted therapy. To determine the most likely compound that can bind to the STEAP2 protein, we docked the modeled STEAP2 3D structure against 2466 FDA (Food and Drug Administration)-approved drug candidates using AutoDock Vina. Protein basic local alignment search tool (BLASTp) search, multiple sequence alignment (MSA), and phylogenetics were further carried out to analyze the diversity of this marker and determine its conserved domains as suitable target regions. Six promising drug candidates (ligands) were identified. Triptorelin had the highest binding energy (−12.1 kcal/mol) followed by leuprolide (docking energy: −11.2 kcal/mol). All the top two drug candidates interacted with residues Ser-372 and Gly-369 in close proximity with the iron-binding domain (an important catalyst of metal reduction). The two drugs had earlier been approved for the treatment of advanced prostate cancer with an elusive mode of action. Through this study, further insight into figuring out their interaction with STEAP2 might be important during treatment.https://www.frontiersin.org/articles/10.3389/fbinf.2022.869375/fullprostate cancermolecular dockingbioinformacticscomputational drug discoverySTEAP2AutoDock Vina |
| spellingShingle | Timothy Ongaba Christian Ndekezi Christian Ndekezi Nana Nakiddu Nana Nakiddu A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates Frontiers in Bioinformatics prostate cancer molecular docking bioinformactics computational drug discovery STEAP2 AutoDock Vina |
| title | A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates |
| title_full | A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates |
| title_fullStr | A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates |
| title_full_unstemmed | A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates |
| title_short | A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates |
| title_sort | molecular docking study of human steap2 for the discovery of new potential anti prostate cancer chemotherapeutic candidates |
| topic | prostate cancer molecular docking bioinformactics computational drug discovery STEAP2 AutoDock Vina |
| url | https://www.frontiersin.org/articles/10.3389/fbinf.2022.869375/full |
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