Protein interfaces

A method for screening for inhibitors of a protein interaction between a first test protein and a second test protein, the method comprising:

• expressing, in a plurality of host cells, a first fusion protein comprising a first test protein and a DNA-binding moiety;
• and
• expressing, in each of the plurality of host cells, a second fusion protein comprising the second test protein and a gene-activating moiety,
• wherein each of the plurality of host cells comprises a plurality of heterologous polynucleotide sequences that each encode a different cytotoxic agent, wherein expression of each of the heterologous polynucleotide sequences that each encode a different cytotoxic agent is under the control of a promoter that has selective affinity for the DNA-binding moiety, wherein interaction between the first test protein and the second test protein causes the gene-activating moiety to activate expression of each of the different cytotoxic agents encoded by each of the plurality of heterologous polynucleotide sequences;
• wherein the DNA-binding moiety is a LexA, cI, Glucocorticoid receptor, TetR, or Ume6 DNA binding moiety;
• wherein the gene activating moiety is a GAL4, B42, or Dof1 gene activating moiety;
• wherein the plurality of different cytotoxic agents are selected from the group consisting of:
• a ribosomally-encoded xenobiotic agent, a ribosomally-encoded poison, a ribosomally-encoded recombinase that excises an essential gene for viability, and any combination thereof.