Essential considerations for using protein–ligand structures in drug discovery
► Quality criteria for identification of reliable protein–ligand structures are presented. ► Electron density is essential for structure evaluation in structure-based drug design. ► High quality structure databases will address clerical errors–20% was observed. ► Iridium quality criteria applied to...
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| Veröffentlicht in: | Drug discovery today 2012-12, Vol.17 (23-24), p.1270-1281 |
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| container_title | Drug discovery today |
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| creator | Warren, Gregory L. Do, Thanh D. Kelley, Brian P. Nicholls, Anthony Warren, Stephen D. |
| description | ► Quality criteria for identification of reliable protein–ligand structures are presented. ► Electron density is essential for structure evaluation in structure-based drug design. ► High quality structure databases will address clerical errors–20% was observed. ► Iridium quality criteria applied to 728 structures – only 17% were high quality. ► All re-refined Iridium structures (highly, mildly and not trustworthy) are available.
Protein–ligand structures are the core data required for structure-based drug design (SBDD). Understanding the error present in this data is essential to the successful development of SBDD tools. Methods for assessing protein–ligand structure quality and a new set of identification criteria are presented here. When these criteria were applied to a set of 728 structures previously used to validate molecular docking software, only 17% were found to be acceptable. Structures were re-refined to maintain internal consistency in the comparison and assessment of the quality criteria. This process resulted in Iridium, a highly trustworthy protein–ligand structure database to be used for development and validation of structure-based design tools for drug discovery.
All structure-based drug design predictions are dependent on the quality of the protein–ligand structure(s) used. This review discusses methods for assessing the quality of this critical data. |
| doi_str_mv | 10.1016/j.drudis.2012.06.011 |
| format | Article |
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Protein–ligand structures are the core data required for structure-based drug design (SBDD). Understanding the error present in this data is essential to the successful development of SBDD tools. Methods for assessing protein–ligand structure quality and a new set of identification criteria are presented here. When these criteria were applied to a set of 728 structures previously used to validate molecular docking software, only 17% were found to be acceptable. Structures were re-refined to maintain internal consistency in the comparison and assessment of the quality criteria. This process resulted in Iridium, a highly trustworthy protein–ligand structure database to be used for development and validation of structure-based design tools for drug discovery.
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Protein–ligand structures are the core data required for structure-based drug design (SBDD). Understanding the error present in this data is essential to the successful development of SBDD tools. Methods for assessing protein–ligand structure quality and a new set of identification criteria are presented here. When these criteria were applied to a set of 728 structures previously used to validate molecular docking software, only 17% were found to be acceptable. Structures were re-refined to maintain internal consistency in the comparison and assessment of the quality criteria. This process resulted in Iridium, a highly trustworthy protein–ligand structure database to be used for development and validation of structure-based design tools for drug discovery.
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Protein–ligand structures are the core data required for structure-based drug design (SBDD). Understanding the error present in this data is essential to the successful development of SBDD tools. Methods for assessing protein–ligand structure quality and a new set of identification criteria are presented here. When these criteria were applied to a set of 728 structures previously used to validate molecular docking software, only 17% were found to be acceptable. Structures were re-refined to maintain internal consistency in the comparison and assessment of the quality criteria. This process resulted in Iridium, a highly trustworthy protein–ligand structure database to be used for development and validation of structure-based design tools for drug discovery.
All structure-based drug design predictions are dependent on the quality of the protein–ligand structure(s) used. This review discusses methods for assessing the quality of this critical data.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>22728777</pmid><doi>10.1016/j.drudis.2012.06.011</doi><tpages>12</tpages></addata></record> |
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| subjects | Binding Sites Biological and medical sciences Crystallography, X-Ray Drug Discovery - methods Drug Discovery - standards General pharmacology Ligands Medical sciences Molecular Docking Simulation - methods Molecular Docking Simulation - standards Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Protein Conformation Proteins - chemistry Software |
| title | Essential considerations for using protein–ligand structures in drug discovery |
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