Computational strategies for PROTAC drug discovery
Proteolysis-targeting chimeras (PROTACs), a novel targeted protein degradation technology for potential clinical drug discovery, is composed of a protein-targeting ligand covalently linked to an E3 ligase ligand. Through recruiting E3 ligase to target proteins, PROTACs elicit ubiquitination and subs...
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| Format: | Article |
| Language: | English |
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Compuscript Ltd
2023-01-01
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| Series: | Acta Materia Medica |
| Online Access: | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2022-0041 |
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| _version_ | 1849420766807851008 |
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| author | Jia Wu Wanhe Wang Chung-Hang Leung |
| author_facet | Jia Wu Wanhe Wang Chung-Hang Leung |
| author_sort | Jia Wu |
| collection | DOAJ |
| description | Proteolysis-targeting chimeras (PROTACs), a novel targeted protein degradation technology for potential clinical drug discovery, is composed of a protein-targeting ligand covalently linked to an E3 ligase ligand. Through recruiting E3 ligase to target proteins, PROTACs elicit ubiquitination and subsequent degradation of targets via the ubiquitin-proteasome system. In the past few decades, molecular docking and virtual screening have emerged as an efficient strategy in drug discovery for identifying compounds from a large database of chemical structures. For PROTACs, molecular docking accurately simulates the protein-PROTAC-E3 ternary complex, thus greatly accelerating structure-activity-relationship analysis, and improving ligand affinity and selectivity. In this review, we summarize recent efforts in the application of molecular docking and virtual screening for PROTAC drug discovery. To date, approximately nine target proteins and twelve PROTACs have been successfully developed through molecular docking and virtual screening. Finally, the potential challenges of molecular docking and virtual screening-based PROTACs are discussed. |
| format | Article |
| id | doaj-art-cb8367166f7b484d9b37f658ec759154 |
| institution | Kabale University |
| issn | 2737-7946 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Compuscript Ltd |
| record_format | Article |
| series | Acta Materia Medica |
| spelling | doaj-art-cb8367166f7b484d9b37f658ec7591542025-08-20T03:31:38ZengCompuscript LtdActa Materia Medica2737-79462023-01-0121425310.15212/AMM-2022-0041Computational strategies for PROTAC drug discoveryJia WuWanhe WangChung-Hang LeungProteolysis-targeting chimeras (PROTACs), a novel targeted protein degradation technology for potential clinical drug discovery, is composed of a protein-targeting ligand covalently linked to an E3 ligase ligand. Through recruiting E3 ligase to target proteins, PROTACs elicit ubiquitination and subsequent degradation of targets via the ubiquitin-proteasome system. In the past few decades, molecular docking and virtual screening have emerged as an efficient strategy in drug discovery for identifying compounds from a large database of chemical structures. For PROTACs, molecular docking accurately simulates the protein-PROTAC-E3 ternary complex, thus greatly accelerating structure-activity-relationship analysis, and improving ligand affinity and selectivity. In this review, we summarize recent efforts in the application of molecular docking and virtual screening for PROTAC drug discovery. To date, approximately nine target proteins and twelve PROTACs have been successfully developed through molecular docking and virtual screening. Finally, the potential challenges of molecular docking and virtual screening-based PROTACs are discussed.https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2022-0041 |
| spellingShingle | Jia Wu Wanhe Wang Chung-Hang Leung Computational strategies for PROTAC drug discovery Acta Materia Medica |
| title | Computational strategies for PROTAC drug discovery |
| title_full | Computational strategies for PROTAC drug discovery |
| title_fullStr | Computational strategies for PROTAC drug discovery |
| title_full_unstemmed | Computational strategies for PROTAC drug discovery |
| title_short | Computational strategies for PROTAC drug discovery |
| title_sort | computational strategies for protac drug discovery |
| url | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2022-0041 |
| work_keys_str_mv | AT jiawu computationalstrategiesforprotacdrugdiscovery AT wanhewang computationalstrategiesforprotacdrugdiscovery AT chunghangleung computationalstrategiesforprotacdrugdiscovery |