Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2.
A major challenge in the field of ligand discovery is to identify chemically useful fragments that can be developed into inhibitors of specific protein-protein interactions. Low molecular weight fragments (with molecular weight less than 250 Da) are likely to bind weakly to a protein's surface....
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0121424 |
| _version_ | 1818725424857874432 |
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| author | Douglas R Houston Li-Hsuan Yen Simon Pettit Malcolm D Walkinshaw |
| author_facet | Douglas R Houston Li-Hsuan Yen Simon Pettit Malcolm D Walkinshaw |
| author_sort | Douglas R Houston |
| collection | DOAJ |
| description | A major challenge in the field of ligand discovery is to identify chemically useful fragments that can be developed into inhibitors of specific protein-protein interactions. Low molecular weight fragments (with molecular weight less than 250 Da) are likely to bind weakly to a protein's surface. Here we use a new virtual screening procedure which uses a combination of similarity searching and docking to identify chemically tractable scaffolds that bind to the p53-interaction site of MDM2. The binding has been verified using capillary electrophoresis which has proven to be an excellent screening method for such small, weakly binding ligands. |
| first_indexed | 2024-12-17T21:42:06Z |
| format | Article |
| id | doaj.art-400af3d3c9bc40dbb710989c2b88c3e8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T21:42:06Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-400af3d3c9bc40dbb710989c2b88c3e82022-12-21T21:31:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012142410.1371/journal.pone.0121424Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2.Douglas R HoustonLi-Hsuan YenSimon PettitMalcolm D WalkinshawA major challenge in the field of ligand discovery is to identify chemically useful fragments that can be developed into inhibitors of specific protein-protein interactions. Low molecular weight fragments (with molecular weight less than 250 Da) are likely to bind weakly to a protein's surface. Here we use a new virtual screening procedure which uses a combination of similarity searching and docking to identify chemically tractable scaffolds that bind to the p53-interaction site of MDM2. The binding has been verified using capillary electrophoresis which has proven to be an excellent screening method for such small, weakly binding ligands.https://doi.org/10.1371/journal.pone.0121424 |
| spellingShingle | Douglas R Houston Li-Hsuan Yen Simon Pettit Malcolm D Walkinshaw Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2. PLoS ONE |
| title | Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2. |
| title_full | Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2. |
| title_fullStr | Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2. |
| title_full_unstemmed | Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2. |
| title_short | Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2. |
| title_sort | structure and ligand based virtual screening identifies new scaffolds for inhibitors of the oncoprotein mdm2 |
| url | https://doi.org/10.1371/journal.pone.0121424 |
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