Patent ID: 7223537

Claim:
A method of performing a high throughput screen to identify whether a test agent has an effect on a biomolecular interaction, comprising: a) introducing nucleic acid constructs encoding a first and a second low affinity reporter subunits into a mammalian cell population and producing an in vitro cultured living mammalian cell population that expresses said first low-affinity reporter subunit coupled to a first putative binding moiety, and said second low affinity reporter subunit coupled to a second putative binding moiety, wherein said first and said second low affinity subunits are mutants of E. coli β-galactosidase that complement one another to form an active E. coli β-galactosidase enzyme when associated in situ in said cultured living mammalian cell population, said association being a biomolecular interaction mediated by said first putative binding moiety; b) incubating the said cultured living mammalian cell population in the presence and absence of said test agent and in the presence of a substrate, wherein said substrate is converted to a detectable product by said active E. coli β-galactosidase enzyme; c) detecting a detectable signal generated from said detectable product; and d) comparing the said detectable signal generated in the presence of said test agent with said detectable signal generated in the absence test agent, wherein a difference in said signals is an indication that the said test agent affects said biomolecular interaction.