Automated NMR fragment based screening identified a novel interface blocker to the LARG/RhoA complex.

ABSTRACT: The small GTPase cycles between the inactive GDP form and the activated GTP form, catalyzed by the upstream guanine exchange factors. The modulation of such process by small molecules has been proven to be a fruitful route for therapeutic intervention to prevent the over-activation of the small GTPase. The fragment based approach emerging in the past decade has demonstrated its paramount potential in the discovery of inhibitors targeting such novel and challenging protein-protein interactions. The details regarding the procedure of NMR fragment screening from scratch have been rarely disclosed comprehensively, thus restricts its wider applications. To achieve a consistent screening applicable to a number of targets, we developed a highly automated protocol to cover every aspect of NMR frag

SUBMITTER: Gao J 

PROVIDER: S-EPMC3914932 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature