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Document Type |
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Thesis |
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Document Title |
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In silico exploration of the first transferrin receptor (TfR1) as a drug target of a rare immunodeficiency case دراسة حاسوبية على المستقبل الأول للترانسفيرين كهدف علاجي لحالة عوز مناعي نادرة |
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Subject |
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Faculty of Science |
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Document Language |
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Arabic |
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Abstract |
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Transferrin receptor protein 1 (TfR1) is an important molecule in anti-cancer therapy. Also, the first natural variant (p.Tyr20His) in TFRC, which codes for TfR1 resulted in a rare combined immunodeficiency (CID). This finding suggests a new role of TfR1 in immunity. Targeted delivery of such therapeutic compounds improves their cellular uptake and circulation time, thereby enhancing therapeutic efficacy. Drug designing is therefore used to engineer molecules with structures that facilitate specific interactions. However, this process requires a thorough knowledge of all the interactions, including the three-dimensional (3D) and quaternary structures (QS) of the interacting molecules. Since structural information is available for only a part of the full TfR1 sequence, in the present study, we predicted the whole structure of TfR1 using homology modelling, docking, and molecular dynamics simulations. Homology modelling is used to generate 3D structures of TfR1 using MODELLER, I-TASSER, and RaptorX programs. Verify3D and Rampage server evaluated the quality of the resultant models. According to this evaluation, the RaptorX model that was validated by Verify3D (compatibility: 83.82%) had (95.5%) of residues within the favoured regions of the Ramachandran plot, making it the most reliable 3D structure compared with others. The QS of TfR1 was built using HADDOCK and SymmDock software, and the results were evaluated by the ligand root mean square deviation (l-RMSD) value computed using the ProFit software. Which showed that both HADDOCK and SymmDock gave acceptable results. However, the HADDOCK result was more stable and closest to the native complex structure with disulfide bonds. Therefore, the HADDOCK complex was further refined using both SymmRef and GalaxyRefineComplex until the medium l-RMSD rank was reached. This QS was successfully verified using nanoscale molecular dynamics (NAMD) energy minimization. This model could pave the way for further functional, structural, and therapeutic studies on TfR1. |
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Supervisor |
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Dr.Hani Mohammed Ali |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1441 AH
2020 AD |
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Co-Supervisor |
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Dr.Rania Marwan Makki |
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Added Date |
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Sunday, May 17, 2020 |
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Researchers
| مها عاتق الرفاعي | AL-Refaei, Maha Ateeq | Researcher | Master | |
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