Modulators of the p53-MDM2 interaction : search for MDM2 interactors using structural guidance
The interaction between MDM2 and p53 is essential for several cellular events, including cell growth, DNA repair, cell cycle arrest and apoptosis. So far, p53 is the only known protein that binds to the hydrophobic pocket of MDM2. In this study, we tried to identify other proteins that also interact...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Final Year Project (FYP) |
| Language: | English |
| Published: |
2014
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/10356/60604 |
| _version_ | 1811683038090756096 |
|---|---|
| author | Lin, Jianqing |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Lin, Jianqing |
| author_sort | Lin, Jianqing |
| collection | NTU |
| description | The interaction between MDM2 and p53 is essential for several cellular events, including cell growth, DNA repair, cell cycle arrest and apoptosis. So far, p53 is the only known protein that binds to the hydrophobic pocket of MDM2. In this study, we tried to identify other proteins that also interact with the p53-binding domain of MDM2 using structural homology for which we use the CLICK method. CLICK is an algorithm for structure comparison and works in a topology-independent manner. Three key residues (F19, W23 and L26) for the MDM2-p53 binding were extracted from p53 and compared against all the available Protein Data Bank (PDB) structures. 15728 candidates were identified by CLICK. A filtering step was performed to reduce the number of candidates to 216, which were then validated via structural analysis and literature searches. In the end, one potential binding protein of MDM2 was identified: human fidgetin-like protein 1 (FIGNL1) has a C-terminal helix that can potentially bind to the hydrophobic pocket of MDM2. Preliminary MD simulations were performed to test the binding between MDM2 and the C-terminal helix of human FIGNL1; the results indicated a stable binding. Our study succeeded in identifying a potential binding protein of MDM2 while demonstrating the effectiveness of CLICK. |
| first_indexed | 2024-10-01T04:06:22Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/60604 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:06:22Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/606042023-02-28T18:06:30Z Modulators of the p53-MDM2 interaction : search for MDM2 interactors using structural guidance Lin, Jianqing School of Biological Sciences A*STAR Bioinformatics Institute Chandra Verma DRNTU::Science The interaction between MDM2 and p53 is essential for several cellular events, including cell growth, DNA repair, cell cycle arrest and apoptosis. So far, p53 is the only known protein that binds to the hydrophobic pocket of MDM2. In this study, we tried to identify other proteins that also interact with the p53-binding domain of MDM2 using structural homology for which we use the CLICK method. CLICK is an algorithm for structure comparison and works in a topology-independent manner. Three key residues (F19, W23 and L26) for the MDM2-p53 binding were extracted from p53 and compared against all the available Protein Data Bank (PDB) structures. 15728 candidates were identified by CLICK. A filtering step was performed to reduce the number of candidates to 216, which were then validated via structural analysis and literature searches. In the end, one potential binding protein of MDM2 was identified: human fidgetin-like protein 1 (FIGNL1) has a C-terminal helix that can potentially bind to the hydrophobic pocket of MDM2. Preliminary MD simulations were performed to test the binding between MDM2 and the C-terminal helix of human FIGNL1; the results indicated a stable binding. Our study succeeded in identifying a potential binding protein of MDM2 while demonstrating the effectiveness of CLICK. Bachelor of Science in Biological Sciences 2014-05-29T02:25:07Z 2014-05-29T02:25:07Z 2014 2014 Final Year Project (FYP) http://hdl.handle.net/10356/60604 en Nanyang Technological University 47 p. application/pdf |
| spellingShingle | DRNTU::Science Lin, Jianqing Modulators of the p53-MDM2 interaction : search for MDM2 interactors using structural guidance |
| title | Modulators of the p53-MDM2 interaction : search for MDM2 interactors using structural guidance |
| title_full | Modulators of the p53-MDM2 interaction : search for MDM2 interactors using structural guidance |
| title_fullStr | Modulators of the p53-MDM2 interaction : search for MDM2 interactors using structural guidance |
| title_full_unstemmed | Modulators of the p53-MDM2 interaction : search for MDM2 interactors using structural guidance |
| title_short | Modulators of the p53-MDM2 interaction : search for MDM2 interactors using structural guidance |
| title_sort | modulators of the p53 mdm2 interaction search for mdm2 interactors using structural guidance |
| topic | DRNTU::Science |
| url | http://hdl.handle.net/10356/60604 |
| work_keys_str_mv | AT linjianqing modulatorsofthep53mdm2interactionsearchformdm2interactorsusingstructuralguidance |