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

ABSTRACT: 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 rate of protein purification and crystallization, but the broad applicability of this approach is unknown. We implemented two screening platforms, based on either fluorimetry or static light scattering, to measure the increase in protein thermal stability upon binding of a ligand without the need to monitor enzyme activity. In total, 221 different proteins from humans and human parasites were screened against one or both of two sorts of small-molecule libraries. The first library comprised different salts, pH conditions, and commonly found small molecules and was applicabl

SUBMITTER: Vedadi M 

PROVIDER: S-EPMC1595307 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature