Structure-based rational design of covalent probes
Abstract Covalent probes are becoming increasingly important to both fundamental biology and drug design, as what was once an idiosyncrasy at best and a source of toxicity at worst has transitioned to a paradigm for drug discovery. However, these covalent probes offer different challenges for the in...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-025-01606-y |
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| _version_ | 1849333164787367936 |
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| author | Matthew Holcomb Manuel Llanos Althea Hansel-Harris Stefano Forli |
| author_facet | Matthew Holcomb Manuel Llanos Althea Hansel-Harris Stefano Forli |
| author_sort | Matthew Holcomb |
| collection | DOAJ |
| description | Abstract Covalent probes are becoming increasingly important to both fundamental biology and drug design, as what was once an idiosyncrasy at best and a source of toxicity at worst has transitioned to a paradigm for drug discovery. However, these covalent probes offer different challenges for the incorporation of structural data into the design process than do non-covalent probes, whose activity may be captured by very few bound states. In this review, we discuss the role of structure-based design in the discovery and optimization of covalent probes, with a special emphasis on computational methods to leverage structural data. |
| format | Article |
| id | doaj-art-2b313043f0294e309e08059190e6e90a |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-2b313043f0294e309e08059190e6e90a2025-08-20T03:45:57ZengNature PortfolioCommunications Chemistry2399-36692025-08-018111210.1038/s42004-025-01606-yStructure-based rational design of covalent probesMatthew Holcomb0Manuel Llanos1Althea Hansel-Harris2Stefano Forli3Department of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteAbstract Covalent probes are becoming increasingly important to both fundamental biology and drug design, as what was once an idiosyncrasy at best and a source of toxicity at worst has transitioned to a paradigm for drug discovery. However, these covalent probes offer different challenges for the incorporation of structural data into the design process than do non-covalent probes, whose activity may be captured by very few bound states. In this review, we discuss the role of structure-based design in the discovery and optimization of covalent probes, with a special emphasis on computational methods to leverage structural data.https://doi.org/10.1038/s42004-025-01606-y |
| spellingShingle | Matthew Holcomb Manuel Llanos Althea Hansel-Harris Stefano Forli Structure-based rational design of covalent probes Communications Chemistry |
| title | Structure-based rational design of covalent probes |
| title_full | Structure-based rational design of covalent probes |
| title_fullStr | Structure-based rational design of covalent probes |
| title_full_unstemmed | Structure-based rational design of covalent probes |
| title_short | Structure-based rational design of covalent probes |
| title_sort | structure based rational design of covalent probes |
| url | https://doi.org/10.1038/s42004-025-01606-y |
| work_keys_str_mv | AT matthewholcomb structurebasedrationaldesignofcovalentprobes AT manuelllanos structurebasedrationaldesignofcovalentprobes AT altheahanselharris structurebasedrationaldesignofcovalentprobes AT stefanoforli structurebasedrationaldesignofcovalentprobes |