Solubility-Weighted Index: fast and accurate prediction of protein solubility

Bikash K. Bhandari; Paul P. Gardner; Chun Shen Lim

High levels of protein expression and solubility are two major requirements of successful recombinant protein production (Esposito and Chatterjee 2006) . However, recombinant protein production is a challenging process. Almost half of recombinant proteins fail to be expressed and half of the successfully expressed proteins are insoluble ( http://targetdb.rcsb.org/metrics/ ). These failures hamper protein research, with particular implications for structural, functional and pharmaceutical studies that require soluble and concentrated protein solutions (Kramer et al. 2012; Hou et al. 2018) . Therefore, solubility prediction and protein engineering for enhanced solubility is an active area of research. Notable protein engineering approaches include mutagenesis, truncation (i.e., expression of partial protein sequences), or fusion with a solubility-enhancing tag (Waldo 2003; Esposito and Chatterjee 2006; Trevino, Martin Scholtz, and Nick Pace 2007; Chan et al. 2010; Kramer et al. 2012; Costa et al. 2014 ) .