Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery
Abstract We present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized a three-dimensional (3D) generative modeling method Pocket2Mol, for the de novo design of molecules...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-03-01
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| Series: | Journal of Cheminformatics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13321-024-00829-w |
| _version_ | 1797247054331772928 |
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| author | Lingling Shen Jian Fang Lulu Liu Fei Yang Jeremy L. Jenkins Peter S. Kutchukian He Wang |
| author_facet | Lingling Shen Jian Fang Lulu Liu Fei Yang Jeremy L. Jenkins Peter S. Kutchukian He Wang |
| author_sort | Lingling Shen |
| collection | DOAJ |
| description | Abstract We present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized a three-dimensional (3D) generative modeling method Pocket2Mol, for the de novo design of molecules in spatial perspective for the targeted protein structures, followed by filters for chemical-physical properties and drug-likeness, structure–activity relationship analysis, and clustering to generate top virtual hit scaffolds. In our WDR5 case study, we acquired a focused set of 2029 compounds after a targeted searching within Novartis archived library based on the virtual scaffolds. Subsequently, we experimentally profiled these compounds, resulting in a novel chemical scaffold series that demonstrated activity in biochemical and biophysical assays. Pocket Crafter successfully prototyped an effective end-to-end 3D generative chemistry-based workflow for the exploration of new chemical scaffolds, which represents a promising approach in early drug discovery for hit identification. |
| first_indexed | 2024-04-24T19:52:35Z |
| format | Article |
| id | doaj.art-3862345979da4f6a9f6a00a5c376a88d |
| institution | Directory Open Access Journal |
| issn | 1758-2946 |
| language | English |
| last_indexed | 2024-04-24T19:52:35Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cheminformatics |
| spelling | doaj.art-3862345979da4f6a9f6a00a5c376a88d2024-03-24T12:32:04ZengBMCJournal of Cheminformatics1758-29462024-03-0116111710.1186/s13321-024-00829-wPocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discoveryLingling Shen0Jian Fang1Lulu Liu2Fei Yang3Jeremy L. Jenkins4Peter S. Kutchukian5He Wang6Novartis Biomedical ResearchNovartis Biomedical ResearchNovartis Biomedical ResearchNovartis Biomedical ResearchNovartis Biomedical ResearchNovartis Biomedical ResearchNovartis Biomedical ResearchAbstract We present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized a three-dimensional (3D) generative modeling method Pocket2Mol, for the de novo design of molecules in spatial perspective for the targeted protein structures, followed by filters for chemical-physical properties and drug-likeness, structure–activity relationship analysis, and clustering to generate top virtual hit scaffolds. In our WDR5 case study, we acquired a focused set of 2029 compounds after a targeted searching within Novartis archived library based on the virtual scaffolds. Subsequently, we experimentally profiled these compounds, resulting in a novel chemical scaffold series that demonstrated activity in biochemical and biophysical assays. Pocket Crafter successfully prototyped an effective end-to-end 3D generative chemistry-based workflow for the exploration of new chemical scaffolds, which represents a promising approach in early drug discovery for hit identification.https://doi.org/10.1186/s13321-024-00829-wHit findingDrug discovery3D generative chemistryWDR5Pocket Crafter |
| spellingShingle | Lingling Shen Jian Fang Lulu Liu Fei Yang Jeremy L. Jenkins Peter S. Kutchukian He Wang Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery Journal of Cheminformatics Hit finding Drug discovery 3D generative chemistry WDR5 Pocket Crafter |
| title | Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery |
| title_full | Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery |
| title_fullStr | Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery |
| title_full_unstemmed | Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery |
| title_short | Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery |
| title_sort | pocket crafter a 3d generative modeling based workflow for the rapid generation of hit molecules in drug discovery |
| topic | Hit finding Drug discovery 3D generative chemistry WDR5 Pocket Crafter |
| url | https://doi.org/10.1186/s13321-024-00829-w |
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