I have a protein that acts as a monomer, but appears to have a relatively high self-affinity in vivo (measured using transient transfection of a plasmid coding for the protein), which is annoying because I'm trying to engineer conditional self-association like with FRB-FKBP w/ rapamycin. Have there been any papers where self-clumping of a protein has been engineered away?
My current approach is to use threading to identify a protein structure and a docking program to identify sites of self-interaction and mutate those sites away.