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

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

Upon further inspection, we observe some interesting properties in SWI. SWI anti-correlates with helix propensity, GRAVY, aromaticity and isoelectric point (Fig 2C and 3) , suggesting that SWI incorporates the key propensities affecting solubility. Amino acid residues with a lower aromaticity or hydrophilic are known to improve protein solubility (Trevino, Martin Scholtz, and Nick Pace 2007; Niwa et al. 2009; Kramer et al. 2012; Warwicker, Charonis, and Curtis 2014; Han et al. 2019; Wilkinson and Harrison 1991) . Consistent with previous studies, the charged residues aspartate (D), glutamate (E) and lysine (K) are associated with high solubility, whereas the aromatic residues phenylalanine (F), tryptophan (W) and tyrosine (Y) are associated with low solubility (Fig 2C and Supplementary Fig S7A) . Cysteine residue (C) has the lowest weight probably because disulfide bonds couldn't be properly formed in the E. coli expression hosts (Stewart, Aslund, and Beckwith 1998; Rosano and Ceccarelli 2014; Jia and Jeon 2016; Aslund and Beckwith 1999) . The weights are likely different if the solubility analysis was done using the reductase-deficient, E. coli Origami host strains, or eukaryotic hosts.