Including Tightly-Bound Water Molecules in de Novo Drug Design. Exemplification through the in Silico Generation of Poly(ADP-ribose)polymerase Ligands
Different strategies for the in silico generation of ligand molecules in the binding site of poly(ADP-ribose)-polymerase (PARP) were studied in order to observe the effect of the targeting and displacement of tightly bound water molecules. Several molecular scaffolds were identified as having bette...
| Main Authors: | , , |
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| Format: | Journal Article |
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American Chemical Society
2005
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| Online Access: | http://hdl.handle.net/20.500.11937/18506 |
| _version_ | 1848749763430711296 |
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| author | Mancera, Ricardo Garcia-Sosa, A. Firth-Clark, S. |
| author_facet | Mancera, Ricardo Garcia-Sosa, A. Firth-Clark, S. |
| author_sort | Mancera, Ricardo |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Different strategies for the in silico generation of ligand molecules in the binding site of poly(ADP-ribose)-polymerase (PARP) were studied in order to observe the effect of the targeting and displacement of tightly bound water molecules. Several molecular scaffolds were identified as having better interactions in the binding site when targeting one or two tightly bound water molecules in the NAD binding site. Energy calculations were conducted in order to assess the ligand-protein and ligand-water-protein interactions of different functional groups of the generated ligands. These calculations were used to evaluate the energetic consequences of the presence of tightly bound water molecules and to identify those that contribute favorably to the binding of ligands. |
| first_indexed | 2025-11-14T07:26:06Z |
| format | Journal Article |
| id | curtin-20.500.11937-18506 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:26:06Z |
| publishDate | 2005 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-185062017-09-13T13:45:16Z Including Tightly-Bound Water Molecules in de Novo Drug Design. Exemplification through the in Silico Generation of Poly(ADP-ribose)polymerase Ligands Mancera, Ricardo Garcia-Sosa, A. Firth-Clark, S. water PARP hydration drug design ligand-protein interactions Different strategies for the in silico generation of ligand molecules in the binding site of poly(ADP-ribose)-polymerase (PARP) were studied in order to observe the effect of the targeting and displacement of tightly bound water molecules. Several molecular scaffolds were identified as having better interactions in the binding site when targeting one or two tightly bound water molecules in the NAD binding site. Energy calculations were conducted in order to assess the ligand-protein and ligand-water-protein interactions of different functional groups of the generated ligands. These calculations were used to evaluate the energetic consequences of the presence of tightly bound water molecules and to identify those that contribute favorably to the binding of ligands. 2005 Journal Article http://hdl.handle.net/20.500.11937/18506 10.1021/ci049694b American Chemical Society restricted |
| spellingShingle | water PARP hydration drug design ligand-protein interactions Mancera, Ricardo Garcia-Sosa, A. Firth-Clark, S. Including Tightly-Bound Water Molecules in de Novo Drug Design. Exemplification through the in Silico Generation of Poly(ADP-ribose)polymerase Ligands |
| title | Including Tightly-Bound Water Molecules in de Novo Drug Design. Exemplification through the in Silico Generation of Poly(ADP-ribose)polymerase Ligands |
| title_full | Including Tightly-Bound Water Molecules in de Novo Drug Design. Exemplification through the in Silico Generation of Poly(ADP-ribose)polymerase Ligands |
| title_fullStr | Including Tightly-Bound Water Molecules in de Novo Drug Design. Exemplification through the in Silico Generation of Poly(ADP-ribose)polymerase Ligands |
| title_full_unstemmed | Including Tightly-Bound Water Molecules in de Novo Drug Design. Exemplification through the in Silico Generation of Poly(ADP-ribose)polymerase Ligands |
| title_short | Including Tightly-Bound Water Molecules in de Novo Drug Design. Exemplification through the in Silico Generation of Poly(ADP-ribose)polymerase Ligands |
| title_sort | including tightly-bound water molecules in de novo drug design. exemplification through the in silico generation of poly(adp-ribose)polymerase ligands |
| topic | water PARP hydration drug design ligand-protein interactions |
| url | http://hdl.handle.net/20.500.11937/18506 |