Protein/Solubility Folding Assessed By Structural Complementation

A method for screening candidate modulator substance that protein aggregate formation comprising:

• a) providing an expression construct comprising (i) a gene encoding fusion protein, said fusion protein comprising an aggregate-forming protein of interest fused to a first segment of a marker protein, wherein said first segment exhibits only systematic effects on the folding or solubility of the protein of interest, and (ii) a promoter active in said host cell and operably linked to said gene;
• b) contacting said fusion protein with a second segment of said marker protein, wherein said second segment is capable of structural complementation with said first segment, wherein contacting takes place in the presence of said candidate modulator substance;
• and
• c) determining structural complementation,
• wherein a relative change in structural complementation, as compared to the structural complementation observed in the absence of said candidate modulator substance, indicates that said candidate modulator substance is a modulator of aggregate formation.