System to detect small molecule/peptide interaction

A method to determine whether a small molecule agent and a target protein interact, said method comprising the steps of:

• a) incubating a recombinant host cell in vitro which contains
• i) a detectable marker expression unit which comprises an inducible promoter operably linked to a nucleotide sequence encoding a detectable marker, wherein the expression of said detectable maker is regulated by said inducible promoter;
• ii) a target protein expression unit which comprises a nucleotide sequence encoding a fusion protein comprising a target protein and a first portion of a transcription activator protein selected from the group consisting of a DNA binding domain and an RNA polymerase activation domain;
• iii) a ligand binding domain expression unit which comprises a nucleotide sequence encoding a fusion protein comprising a ligand binding domain and a second portion of a transcription activator protein selected from the group consisting of a DNA binding domain and an RNA polymerase activation domain, whichever is not employed in (ii);
• and
• iv) a small molecule agent/ligand complex wherein said ligand binds to said ligand-binding domain;
• under conditions in which said expression units (ii) and (iii) are expressed;
• b) detecting whether said detectable marker is expressed;
• and
• c) determining the level of binding of said agent to said target protein by the level of expression of said detectable marker.