Promiscuous Binders

The term promiscous binder in a Screening context refers to small molecule ligands which display unspecfific effects toward the Target molecule. These binders can show up in screenings as a Hit, while being in fact false-positives. Promiscous binders can be identified by TRIC, based on several observations: First, promiscous binders can induce target Aggregation, which is indicated by the appearance of irregular TRIC-trace and Well-Scan Quality issues at higher ligand concentrations. This can either result from aggregation of the Ligand itself or an induction of target aggregation. Second, over-stoichiometric (unspecific) binding of a promiscuous binder to the target molecule can be identified based on dose response curves which do not reflect a 1:1 stoichiometry. In this case, fitting of the data with the Hill Model yields Hill coefficients > 1.