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

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

We sought to understand what makes a protein soluble, and develop a fast and accurate approach for solubility prediction. To determine which protein sequence properties accurately predict protein solubility, we analysed 12,216 target proteins from over 196 species that were expressed in E. coli (the PSI:Biology dataset; see Supplementary Fig S1 and Table S1A ) (Chen et al. 2004; Acton et al. 2005) . These proteins were expressed either with a C-terminal or N-terminal polyhistidine fusion tag (pET21_NESG and pET15_NESG expression vectors, N=8,780 and 3,436, respectively). They were previously curated and labeled as 'Protein_Soluble' or 'Tested_Not_Soluble' (Seiler et al. 2014) , based on the soluble analysis of cell lysate using SDS-PAGE (R. Xiao et al. 2010) . A total of 8,238 recombinant proteins were found to be soluble, in which 6,432 of them belong to the pET21_NESG dataset. Both the expression system and solubility analysis method are commonly used (Costa et al. 2014) . Therefore, this collection of data captures a broad range of protein solubility issues.