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

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

We conclude that SWI is a well-balanced index that is derived from a simple sequence composition scoring method. To demonstrate the usefulness of SWI, we developed a web server called SoDoPE (Soluble Domain for Protein Expression; https://tisigner.com/sodope ). SoDoPE calculates the probability of solubility of a user-selected region based on SWI, which can either be a full-length or a partial sequence (see Methods and Supplementary Table S8 ). This implementation is based on our observation that some protein domains tend to be more soluble than the others. To demonstrate this point, we have analysed three commercial monoclonal antibodies and the severe acute respiratory syndrome coronavirus proteomes (SARS-CoV and SARS-CoV-2) (Wang et al. 2009; Marra et al. 2003; F. Wu et al. 2020) (Supplementary Fig S8 and S9 ). These soluble domains may enhance protein solubility as a whole. SoDoPE also provides options for solubility prediction at the presence of solubility fusion tags. Similarly, solubility tags may act as soluble 'protein domains' that can outweigh the aggregation propensity of insoluble proteins. However, some soluble fusion proteins may become insoluble after proteolytic cleavage of solubility tags (Lebendiker and Danieli 2014) . In addition, SoDoPE is integrated with TIsigner, a gene optimisation web service for protein expression. This pipeline provides a holistic approach to improve the outcome of recombinant protein expression.