Essential considerations for using protein-ligand structures in drug discovery.
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.
OpenEye Scientific Software, Inc., Santa Fe, NM 87508, USA. greg@eyesopen.com
Gregory L
GL
Warren
Thanh D
TD
Do
Brian P
BP
Kelley
Anthony
A
Nicholls
Stephen D
SD
Warren
D001665:Binding Sites; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods* / Q000592:standards; D008024:Ligands; D062105:Molecular Docking Simulation / Q000379:methods* / Q000592:standards; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012984:Software
D008024:Ligands; D011506:Proteins