TWN-FS method: A novel fragment screening method for drug discovery
Fragment-based drug discovery (FBDD) is a well-established and effective method for generating diverse and novel hits in drug design. Kinases are suitable targets for FBDD due to their well-defined structure. Water molecules contribute to structure and function of proteins and also influence the env...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023003495 |
| _version_ | 1797384100213948416 |
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| author | Hye Ree Yoon Gyoung Jin Park Anand Balupuri Nam Sook Kang |
| author_facet | Hye Ree Yoon Gyoung Jin Park Anand Balupuri Nam Sook Kang |
| author_sort | Hye Ree Yoon |
| collection | DOAJ |
| description | Fragment-based drug discovery (FBDD) is a well-established and effective method for generating diverse and novel hits in drug design. Kinases are suitable targets for FBDD due to their well-defined structure. Water molecules contribute to structure and function of proteins and also influence the environment within the binding pocket. Water molecules form a variety of hydrogen-bonded cyclic water-ring networks, collectively known as topological water networks (TWNs). Analyzing the TWNs in protein binding sites can provide valuable insights into potential locations and shapes for fragments within the binding site. Here, we introduce TWN-based fragment screening (TWN-FS) method, a novel screening method that suggests fragments through grouped TWN analysis within the protein binding site. We used this method to screen known CDK2, CHK1, IGF1R and ERBB4 inhibitors. Our findings suggest that TWN-FS method has the potential to effectively screen fragments. The TWN-FS method package is available on GitHub at https://github.com/pkj0421/TWN-FS. |
| first_indexed | 2024-03-08T21:30:37Z |
| format | Article |
| id | doaj.art-dbec0ba4ba10433aacddf2d048c46fd7 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:30:37Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-dbec0ba4ba10433aacddf2d048c46fd72023-12-21T07:32:14ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012146834696TWN-FS method: A novel fragment screening method for drug discoveryHye Ree Yoon0Gyoung Jin Park1Anand Balupuri2Nam Sook Kang3Graduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South KoreaGraduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South KoreaGraduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South KoreaCorresponding author.; Graduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South KoreaFragment-based drug discovery (FBDD) is a well-established and effective method for generating diverse and novel hits in drug design. Kinases are suitable targets for FBDD due to their well-defined structure. Water molecules contribute to structure and function of proteins and also influence the environment within the binding pocket. Water molecules form a variety of hydrogen-bonded cyclic water-ring networks, collectively known as topological water networks (TWNs). Analyzing the TWNs in protein binding sites can provide valuable insights into potential locations and shapes for fragments within the binding site. Here, we introduce TWN-based fragment screening (TWN-FS) method, a novel screening method that suggests fragments through grouped TWN analysis within the protein binding site. We used this method to screen known CDK2, CHK1, IGF1R and ERBB4 inhibitors. Our findings suggest that TWN-FS method has the potential to effectively screen fragments. The TWN-FS method package is available on GitHub at https://github.com/pkj0421/TWN-FS.http://www.sciencedirect.com/science/article/pii/S2001037023003495Water networkHot spotsFragment screeningFragment-based drug designCDK2 |
| spellingShingle | Hye Ree Yoon Gyoung Jin Park Anand Balupuri Nam Sook Kang TWN-FS method: A novel fragment screening method for drug discovery Computational and Structural Biotechnology Journal Water network Hot spots Fragment screening Fragment-based drug design CDK2 |
| title | TWN-FS method: A novel fragment screening method for drug discovery |
| title_full | TWN-FS method: A novel fragment screening method for drug discovery |
| title_fullStr | TWN-FS method: A novel fragment screening method for drug discovery |
| title_full_unstemmed | TWN-FS method: A novel fragment screening method for drug discovery |
| title_short | TWN-FS method: A novel fragment screening method for drug discovery |
| title_sort | twn fs method a novel fragment screening method for drug discovery |
| topic | Water network Hot spots Fragment screening Fragment-based drug design CDK2 |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023003495 |
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