Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination.

摘要: The 3D structures of human therapeutic targets are enabling for drug discovery. However, their purification and crystallization remain rate determining. In individual cases, ligands have been used to increase the success protein crystallization, but broad applicability this approach is unknown. We implemented two screening platforms, based on either fluorimetry or static light scattering, measure in thermal stability upon binding a ligand without need monitor enzyme activity. total, 221 different proteins from humans parasites were screened against one both sorts small-molecule libraries. first library comprised salts, pH conditions, commonly found small molecules was applicable all proteins. second compounds specific families particular interest (e.g., kinases). 20 including nine unique kinases, molecule identified that stabilized promoted structure determination. methods cost-effective, can be any laboratory, promise rates purifying crystallizing significantly, identify new these