Fusion protein technology has been creatively applied to solve many problems encountered in the study of protein structure and function (1,2). One prevalent application is the use of fusion proteins to improve protein expression in Escherichia coli and provide convenient methods for affinity-based protein purification. In many instances, when a foreign protein is overexpressed at high levels in E. coli, the majority of the protein is present as insoluble inclusion bodies. Previous research experience with fusion proteins containing glutathione S-transferase (GST) (3), maltose binding protein (MBP) (4), and thioredoxin (5) has shown that these proteins can improve the expression and solubility of many heterologous proteins. However, improvements in protein expression and solubility are not always guaranteed with these systems. The purpose of our recent research (6) has been to use a combination of protein solubility modeling, bioinformatics, and molecular biology techniques to systematically identify native E. coli proteins which have maximal potential for increasing recombinant fusion protein solubility.