SolubiS: Optimizing Protein Solubility by Minimal Point Mutations

Methods Mol Biol. 2019:1873:317-333. doi: 10.1007/978-1-4939-8820-4_21.


Protein solubility is adapted to endogeneous protein abundance in the cell where protein folding is also assisted by multiple chaperones. During recombinant protein production, purification and storage proteins are frequently handled at concentrations that are several orders of magnitude above their physiological concentration, often resulting in protein aggregation. Here we describe SolubiS, a method allowing for (1) detection of aggregation prone linear segments within a protein sequence and (2) identification of mutations that abolish the aggregation propensity of these segments without affecting the thermodynamic stability of the protein. Provided the availability of structural information this method is applicable to all globular proteins including antibodies, resulting both in increased in vitro protein solubility and in better protein production yields.

Keywords: Protein aggregation; Protein design; SolubiS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Models, Molecular
  • Mutation*
  • Protein Binding
  • Protein Conformation
  • Protein Engineering* / methods
  • Protein Folding
  • Protein Interaction Domains and Motifs
  • Protein Stability
  • Proteins / chemistry*
  • Proteins / genetics*
  • Reproducibility of Results
  • Solubility
  • Structure-Activity Relationship


  • Proteins