Computational identification of anti-cancer compounds targeting the RNA-binding domain of human FOX-1 protein (RBFOX1)
The transcription factor RBFOX1 is essential for cellular proliferation and has shown upregulation in many human cancers. The overexpression of this gene correlates with the motility of cancer cells, their ability to invade surrounding tissues. The aforementioned processes are pivotal in cancer prog...
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| Format: | Article |
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Elsevier
2025-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624007008 |
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| author | Muhammad Tahir ul Qamar Pablo Sanz-Jimenez Shaima Rabeea Banoon Xi-Tong Zhu Fahad M. Aldakheel Nahlah Makki Almansour Leen A. Aldaiji Wafa Abdullah I. Al-Megrin Faisal Ahmad |
| author_facet | Muhammad Tahir ul Qamar Pablo Sanz-Jimenez Shaima Rabeea Banoon Xi-Tong Zhu Fahad M. Aldakheel Nahlah Makki Almansour Leen A. Aldaiji Wafa Abdullah I. Al-Megrin Faisal Ahmad |
| author_sort | Muhammad Tahir ul Qamar |
| collection | DOAJ |
| description | The transcription factor RBFOX1 is essential for cellular proliferation and has shown upregulation in many human cancers. The overexpression of this gene correlates with the motility of cancer cells, their ability to invade surrounding tissues. The aforementioned processes are pivotal in cancer progression, making RBFOX1 a significant target for innovative cancer therapies. The present study seeks to identify new inhibitor compounds that obstruct the biological processes of the target protein associated with cancer. Results shows that control (3S,5aS,6R,8aS,9R,10S,12R,12aS)-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-ol (artenimol) reflecting the binding affinities of −7.9 kcal/mol, Top1 (4-[[2-butyl-5-[(E)-2-carboxy-3-thiophen-2-ylprop-1-enyl]imidazol-1-yl]methyl]benzoic acid) shows −8.7 kcal/mol and Top2 (R)-1-carboxy-5-((S)-2-((2R,4S)-4-carboxy-5,5-dimethylthiazolidin-2-yl)-2-(2-phenylacetamido)acetamido)pentan-1-aminium indicating −8.2 k cal/mol. Additional, molecular dynamic simulation studies shows significant stability during RMSD and RMSF analyses over a 100 ns timescale. Binding domain residues i.e. Phe52, Arg10, Thr84, Ala85 and Arg86 has demonstrated the stability of the system due to robust hydrogen bonds. All of the top hit inhibitor exhibited more stability in comparison to the control inhibitor, where it penetrated deeply, as depicted in PCA analysis. Binding energies and Waterswap calculations significantly refines our comprehensive simulation model. Consequently, our findings provide a potential framework for researchers to further explore in vivo and in vitro analyses of inhibitors targeting the HBFOX1 gene, representing a potential advancement in cancer treatment. |
| format | Article |
| id | doaj-art-b348a8d4acd94058adfaaefbe845f1bd |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Results in Chemistry |
| spelling | doaj-art-b348a8d4acd94058adfaaefbe845f1bd2025-01-29T05:00:53ZengElsevierResults in Chemistry2211-71562025-01-0113102004Computational identification of anti-cancer compounds targeting the RNA-binding domain of human FOX-1 protein (RBFOX1)Muhammad Tahir ul Qamar0Pablo Sanz-Jimenez1Shaima Rabeea Banoon2Xi-Tong Zhu3Fahad M. Aldakheel4Nahlah Makki Almansour5Leen A. Aldaiji6Wafa Abdullah I. Al-Megrin7Faisal Ahmad8State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, ChinaNational Key Laboratory of Crop Genetic Improvement, College of Informatics, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Biology, College of Science, University of Misan, Maysan, IraqState Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China; National Key Laboratory of Crop Genetic Improvement, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China; Corresponding author at: State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China.Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi ArabiaDepartment of Biology, College of Science, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi ArabiaDepartment of Laboratory & Blood Bank, Dr. Sulaiman Al Habib Medical Group, Qassim 51431, Saudi ArabiaDepartment of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi ArabiaFoundation University Medical College, Foundation University Islamabad, Islamabad 44000, Pakistan; School of Biology, Georgia Institute of Technology, Atlanta, GA 30332-0230 USA; Corresponding author at: Foundation University Medical College, Foundation University Islamabad, Islamabad 44000, Pakistan.The transcription factor RBFOX1 is essential for cellular proliferation and has shown upregulation in many human cancers. The overexpression of this gene correlates with the motility of cancer cells, their ability to invade surrounding tissues. The aforementioned processes are pivotal in cancer progression, making RBFOX1 a significant target for innovative cancer therapies. The present study seeks to identify new inhibitor compounds that obstruct the biological processes of the target protein associated with cancer. Results shows that control (3S,5aS,6R,8aS,9R,10S,12R,12aS)-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-ol (artenimol) reflecting the binding affinities of −7.9 kcal/mol, Top1 (4-[[2-butyl-5-[(E)-2-carboxy-3-thiophen-2-ylprop-1-enyl]imidazol-1-yl]methyl]benzoic acid) shows −8.7 kcal/mol and Top2 (R)-1-carboxy-5-((S)-2-((2R,4S)-4-carboxy-5,5-dimethylthiazolidin-2-yl)-2-(2-phenylacetamido)acetamido)pentan-1-aminium indicating −8.2 k cal/mol. Additional, molecular dynamic simulation studies shows significant stability during RMSD and RMSF analyses over a 100 ns timescale. Binding domain residues i.e. Phe52, Arg10, Thr84, Ala85 and Arg86 has demonstrated the stability of the system due to robust hydrogen bonds. All of the top hit inhibitor exhibited more stability in comparison to the control inhibitor, where it penetrated deeply, as depicted in PCA analysis. Binding energies and Waterswap calculations significantly refines our comprehensive simulation model. Consequently, our findings provide a potential framework for researchers to further explore in vivo and in vitro analyses of inhibitors targeting the HBFOX1 gene, representing a potential advancement in cancer treatment.http://www.sciencedirect.com/science/article/pii/S2211715624007008GliomaHBFOX1 geneMolecular modelingMD simulationsWaterswap calculations |
| spellingShingle | Muhammad Tahir ul Qamar Pablo Sanz-Jimenez Shaima Rabeea Banoon Xi-Tong Zhu Fahad M. Aldakheel Nahlah Makki Almansour Leen A. Aldaiji Wafa Abdullah I. Al-Megrin Faisal Ahmad Computational identification of anti-cancer compounds targeting the RNA-binding domain of human FOX-1 protein (RBFOX1) Results in Chemistry Glioma HBFOX1 gene Molecular modeling MD simulations Waterswap calculations |
| title | Computational identification of anti-cancer compounds targeting the RNA-binding domain of human FOX-1 protein (RBFOX1) |
| title_full | Computational identification of anti-cancer compounds targeting the RNA-binding domain of human FOX-1 protein (RBFOX1) |
| title_fullStr | Computational identification of anti-cancer compounds targeting the RNA-binding domain of human FOX-1 protein (RBFOX1) |
| title_full_unstemmed | Computational identification of anti-cancer compounds targeting the RNA-binding domain of human FOX-1 protein (RBFOX1) |
| title_short | Computational identification of anti-cancer compounds targeting the RNA-binding domain of human FOX-1 protein (RBFOX1) |
| title_sort | computational identification of anti cancer compounds targeting the rna binding domain of human fox 1 protein rbfox1 |
| topic | Glioma HBFOX1 gene Molecular modeling MD simulations Waterswap calculations |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624007008 |
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