National Center for
4XNC: Crystal Structure At Room Temperature Of Cyclophilin D In Complex With An Inhibitor
Combining `dry' co-crystallization and in situ diffraction to facilitate ligand screening by X-ray crystallography
Acta Crystallogr. D Biol. Crystallogr. (2015) 71 p.1777-1787
X-ray crystallography is an established technique for ligand screening in fragment-based drug-design projects, but the required manual handling steps - soaking crystals with ligand and the subsequent harvesting - are tedious and limit the throughput of the process. Here, an alternative approach is reported: crystallization plates are pre-coated with potential binders prior to protein crystallization and X-ray diffraction is performed directly `in situ' (or in-plate). Its performance is demonstrated on distinct and relevant therapeutic targets currently being studied for ligand screening by X-ray crystallography using either a bending-magnet beamline or a rotating-anode generator. The possibility of using DMSO stock solutions of the ligands to be coated opens up a route to screening most chemical libraries.