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.