CSAlign and CSAlign-Dock: Structure alignment of ligands considering full flexibility and application to protein–ligand docking
Structure prediction of protein–ligand complexes, called protein–ligand docking, is a critical computational technique that can be used to understand the underlying principle behind the protein functions at the atomic level and to design new molecules regulating the functions. Protein-ligand docking...
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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/S2001037022005414 |
| _version_ | 1797384124840804352 |
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| author | Sohee Kwon Chaok Seok |
| author_facet | Sohee Kwon Chaok Seok |
| author_sort | Sohee Kwon |
| collection | DOAJ |
| description | Structure prediction of protein–ligand complexes, called protein–ligand docking, is a critical computational technique that can be used to understand the underlying principle behind the protein functions at the atomic level and to design new molecules regulating the functions. Protein-ligand docking methods have been employed in structure-based drug discovery for hit discovery and lead optimization. One of the important technical challenges in protein–ligand docking is to account for protein conformational changes induced by ligand binding. A small change such as a single side-chain rotation upon ligand binding can hinder accurate docking. Here we report an increase in docking performance achieved by structure alignment to known complex structures. First, a fully flexible compound-to-compound alignment method CSAlign is developed by global optimization of a shape score. Next, the alignment method is combined with a docking algorithm to dock a new ligand to a target protein when a reference protein–ligand complex structure is available. This alignment-based docking method, called CSAlign-Dock, showed superior performance to ab initio docking methods in cross-docking benchmark tests. Both CSAlign and CSAlign-Dock are freely available as a web server at https://galaxy.seoklab.org/csalign. |
| first_indexed | 2024-03-08T21:30:58Z |
| format | Article |
| id | doaj.art-3d8f5bd0e38d4635aebedf6fef116a26 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:30:58Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-3d8f5bd0e38d4635aebedf6fef116a262023-12-21T07:30:14ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-0121110CSAlign and CSAlign-Dock: Structure alignment of ligands considering full flexibility and application to protein–ligand dockingSohee Kwon0Chaok Seok1Department of Chemistry, Seoul National University, Seoul 08826, South Korea; Galux Inc, Seoul 08738, South KoreaDepartment of Chemistry, Seoul National University, Seoul 08826, South Korea; Galux Inc, Seoul 08738, South Korea; Corresponding author.Structure prediction of protein–ligand complexes, called protein–ligand docking, is a critical computational technique that can be used to understand the underlying principle behind the protein functions at the atomic level and to design new molecules regulating the functions. Protein-ligand docking methods have been employed in structure-based drug discovery for hit discovery and lead optimization. One of the important technical challenges in protein–ligand docking is to account for protein conformational changes induced by ligand binding. A small change such as a single side-chain rotation upon ligand binding can hinder accurate docking. Here we report an increase in docking performance achieved by structure alignment to known complex structures. First, a fully flexible compound-to-compound alignment method CSAlign is developed by global optimization of a shape score. Next, the alignment method is combined with a docking algorithm to dock a new ligand to a target protein when a reference protein–ligand complex structure is available. This alignment-based docking method, called CSAlign-Dock, showed superior performance to ab initio docking methods in cross-docking benchmark tests. Both CSAlign and CSAlign-Dock are freely available as a web server at https://galaxy.seoklab.org/csalign.http://www.sciencedirect.com/science/article/pii/S2001037022005414Structure alignmentProtein–ligand dockingVirtual screeningStructure-based drug discovery |
| spellingShingle | Sohee Kwon Chaok Seok CSAlign and CSAlign-Dock: Structure alignment of ligands considering full flexibility and application to protein–ligand docking Computational and Structural Biotechnology Journal Structure alignment Protein–ligand docking Virtual screening Structure-based drug discovery |
| title | CSAlign and CSAlign-Dock: Structure alignment of ligands considering full flexibility and application to protein–ligand docking |
| title_full | CSAlign and CSAlign-Dock: Structure alignment of ligands considering full flexibility and application to protein–ligand docking |
| title_fullStr | CSAlign and CSAlign-Dock: Structure alignment of ligands considering full flexibility and application to protein–ligand docking |
| title_full_unstemmed | CSAlign and CSAlign-Dock: Structure alignment of ligands considering full flexibility and application to protein–ligand docking |
| title_short | CSAlign and CSAlign-Dock: Structure alignment of ligands considering full flexibility and application to protein–ligand docking |
| title_sort | csalign and csalign dock structure alignment of ligands considering full flexibility and application to protein ligand docking |
| topic | Structure alignment Protein–ligand docking Virtual screening Structure-based drug discovery |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022005414 |
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