Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting
The transcription factor p53 plays pivotal roles in numerous biological processes, including the suppression of tumours. The rich availability of biophysical data aimed at understanding its structure–function relationships since the 1990s has enabled the application of a variety of computational mod...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10356/83525 http://hdl.handle.net/10220/49762 |
| _version_ | 1826119834442661888 |
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| author | Tan, Yaw Sing Mhoumadi, Yasmina Verma, Chandra Shekhar |
| author2 | Lane, David P |
| author_facet | Lane, David P Tan, Yaw Sing Mhoumadi, Yasmina Verma, Chandra Shekhar |
| author_sort | Tan, Yaw Sing |
| collection | NTU |
| description | The transcription factor p53 plays pivotal roles in numerous biological processes, including the suppression of tumours. The rich availability of biophysical data aimed at understanding its structure–function relationships since the 1990s has enabled the application of a variety of computational modelling techniques towards the establishment of mechanistic models. Together they have provided deep insights into the structure, mechanics, energetics, and dynamics of p53. In parallel, the observation that mutations in p53 or changes in its associated pathways characterize several human cancers has resulted in a race to develop therapeutic modulators of p53, some of which have entered clinical trials. This review describes how computational modelling has played key roles in understanding structural-dynamic aspects of p53, formulating hypotheses about domains that are beyond current experimental investigations, and the development of therapeutic molecules that target the p53 pathway. |
| first_indexed | 2024-10-01T05:06:54Z |
| format | Journal Article |
| id | ntu-10356/83525 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:06:54Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/835252023-02-28T16:59:26Z Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting Tan, Yaw Sing Mhoumadi, Yasmina Verma, Chandra Shekhar Lane, David P School of Biological Sciences Science::Biological sciences p53 Structure The transcription factor p53 plays pivotal roles in numerous biological processes, including the suppression of tumours. The rich availability of biophysical data aimed at understanding its structure–function relationships since the 1990s has enabled the application of a variety of computational modelling techniques towards the establishment of mechanistic models. Together they have provided deep insights into the structure, mechanics, energetics, and dynamics of p53. In parallel, the observation that mutations in p53 or changes in its associated pathways characterize several human cancers has resulted in a race to develop therapeutic modulators of p53, some of which have entered clinical trials. This review describes how computational modelling has played key roles in understanding structural-dynamic aspects of p53, formulating hypotheses about domains that are beyond current experimental investigations, and the development of therapeutic molecules that target the p53 pathway. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2019-08-23T04:43:03Z 2019-12-06T15:24:51Z 2019-08-23T04:43:03Z 2019-12-06T15:24:51Z 2019 Journal Article Tan, Y. S., Mhoumadi, Y., & Verma, C. S. (2019). Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting. Journal of Molecular Cell Biology, 11(4), 306-316. doi:10.1093/jmcb/mjz009 1674-2788 https://hdl.handle.net/10356/83525 http://hdl.handle.net/10220/49762 10.1093/jmcb/mjz009 en Journal of Molecular Cell Biology © 2019 The Author(s). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 11 p. application/pdf |
| spellingShingle | Science::Biological sciences p53 Structure Tan, Yaw Sing Mhoumadi, Yasmina Verma, Chandra Shekhar Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting |
| title | Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting |
| title_full | Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting |
| title_fullStr | Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting |
| title_full_unstemmed | Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting |
| title_short | Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting |
| title_sort | roles of computational modelling in understanding p53 structure biology and its therapeutic targeting |
| topic | Science::Biological sciences p53 Structure |
| url | https://hdl.handle.net/10356/83525 http://hdl.handle.net/10220/49762 |
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