The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors
We have determined the effects that tightly bound water molecules have on the de novo design of cyclin-dependent kinase-2 (CDK2) ligands. In particular, we have analyzed the impact of a specific structural water molecule on the chemical diversity and binding mode of ligands generated through a de no...
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| Format: | Journal Article |
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Springer
2006
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| Online Access: | http://hdl.handle.net/20.500.11937/29203 |
| _version_ | 1848752741215633408 |
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| author | Garcia-sosa, A. Mancera, Ricardo |
| author_facet | Garcia-sosa, A. Mancera, Ricardo |
| author_sort | Garcia-sosa, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | We have determined the effects that tightly bound water molecules have on the de novo design of cyclin-dependent kinase-2 (CDK2) ligands. In particular, we have analyzed the impact of a specific structural water molecule on the chemical diversity and binding mode of ligands generated through a de novo structure-based ligand generation method in the binding site of CDK2. The tightly bound water molecule modifies the size and shape of the binding site and we have found that it also imposed constraints on the observed binding modes of the generated ligands. This in turn had the indirect effect of reducing the chemical diversity of the underlying molecular scaffolds that were able to bind to the enzyme satisfactorily. |
| first_indexed | 2025-11-14T08:13:26Z |
| format | Journal Article |
| id | curtin-20.500.11937-29203 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:13:26Z |
| publishDate | 2006 |
| publisher | Springer |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-292032018-10-03T07:30:50Z The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors Garcia-sosa, A. Mancera, Ricardo Structure-based - drug design Hydration Solvation CDK2 We have determined the effects that tightly bound water molecules have on the de novo design of cyclin-dependent kinase-2 (CDK2) ligands. In particular, we have analyzed the impact of a specific structural water molecule on the chemical diversity and binding mode of ligands generated through a de novo structure-based ligand generation method in the binding site of CDK2. The tightly bound water molecule modifies the size and shape of the binding site and we have found that it also imposed constraints on the observed binding modes of the generated ligands. This in turn had the indirect effect of reducing the chemical diversity of the underlying molecular scaffolds that were able to bind to the enzyme satisfactorily. 2006 Journal Article http://hdl.handle.net/20.500.11937/29203 10.1007/s00894-005-0063-1 Springer fulltext |
| spellingShingle | Structure-based - drug design Hydration Solvation CDK2 Garcia-sosa, A. Mancera, Ricardo The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors |
| title | The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors |
| title_full | The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors |
| title_fullStr | The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors |
| title_full_unstemmed | The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors |
| title_short | The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors |
| title_sort | effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of cdk2 inhibitors |
| topic | Structure-based - drug design Hydration Solvation CDK2 |
| url | http://hdl.handle.net/20.500.11937/29203 |