Patent ID: 7083918

Claim:
A method for identifying a molecule that binds a known target receptor in a bacterial cell from a pool of candidate molecules, comprising: (a) forming a dimeric molecule by covalently bonding each molecule in the pool of candidate molecules to a ligand capable of selectively binding to a receptor; (b) introducing the dimeric molecule into a bacterial cell culture comprising bacterial cells that express a first fusion protein which comprises the known target receptor domain against which the candidate molecule is screened, a second fusion protein which comprises the receptor domain to which the ligand selectively binds, and a reporter gene wherein expression of the reporter gene is conditioned on the proximity of the first fusion protein to the second fusion protein; (c) permitting the dimeric molecule to bind to the first fusion protein and to the second fusion protein, bringing the two fusion proteins into proximity so as to activate the expression of the reporter gene; (d) selecting the bacterial cell that expresses the reporter gene; and (e) identifying the small molecule that binds the known target receptor.