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

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

Higher helix propensity has been reported to increase solubility (Idicula- Thomas and Balaji 2005; Huang et al. 2012 ) . However, our analysis has shown that helical and turn propensities anti-correlate with solubility, whereas sheet propensity lacks correlation with solubility, suggesting that disordered regions may tend to be more soluble (Fig 3) . In accordance with these, SWI has stronger negative correlations with helix and turn propensities. These findings also suggest that protein solubility can be largely explained by overall amino acid composition, not just the surface amino acid residues. This idea aligns with our understanding that protein solubility and folding are closely linked, and folding occurs cotranscriptionally, a complex process that is driven various intrinsic and extrinsic factors (Wilkinson and Harrison 1991; Chiti et al. 2003; Tartaglia et al. 2004; Diaz et al. 2010) . However, it is unclear why sheet propensity has little contribution to solubility because β-sheets have been shown to link closely with protein aggregation (Idicula-Thomas and Balaji 2005) .