Solubility-Weighted Index: Fast And Accurate Prediction Of Protein Solubility

Motivation: Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can therefore be purified.Results: We have discovered that global structural flexibility, which can be modeled by normalized B-factors, accurately predicts the solubility of 12 216 recombinant proteins expressed in Escherichia coll. We have optimized these B-factors, and derived a new set of values for solubility scoring that further improves prediction accuracy. We call this new predictor the 'Solubility-Weighted Index' (SWI). Importantly, SWI outperforms many existing protein solubility prediction tools. Furthermore, we have developed 'SoDoPE' (Soluble Domain for Protein Expression), a web interface that allows users to choose a protein region of interest for predicting and maximizing both protein expression and solubility.