Cited by 495Protein Structure and DynamicsProtein purification and stabilityEnzyme Structure and Function

The CamSol method of rational design of protein mutants with enhanced solubility

Sormanni, Pietro, Aprile, Francesco A., Vendruscolo, Michele·2015·Journal of Molecular Biology

Abstract

Protein solubility is often an essential requirement in biotechnological and biomedical applications. Great advances in understanding the principles that determine this specific property of proteins have been made during the past decade, in particular concerning the physicochemical characteristics of their constituent amino acids. By exploiting these advances, we present the CamSol method for the rational design of protein variants with enhanced solubility. The method works by performing a rapid computational screening of tens of thousand of mutations to identify those with the greatest impact on the solubility of the target protein while maintaining its native state and biological activity. The application to a single-domain antibody that targets the Alzheimer's Aβ peptide demonstrates that the method predicts with great accuracy solubility changes upon mutation, thus offering a cost-effective strategy to help the production of soluble proteins for academic and industrial purposes.

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Crossref · 10.1016/j.jmb.2014.09.026

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  • To predict the solubility and aggregation propensity of protein, several prediction tools have been developed, such as Camsol and SOLart, with SOLart currently holding state-of-the-art performance.

    “To predict the solubility and aggregation propensity of protein, several prediction tools have been developed, such as the Camsol [25], and SOLart [26], with SOLart currently holding state-of-the-art performance.”
  • Good solubility is crucial to avoid aggregation that can potentially lead to loss of activity, degradation of antibodies or immunogenicity.

    “Good solubility is crucial [202, 203] to avoid aggregation that can potentially lead to loss of activity, degradation of antibodies or immunogenicity, as discussed previously.”

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Authors
Sormanni, P., Aprile, F. A., & Vendruscolo, M.
Affiliations
University of Cambridge (GB)
Corresponding author
Vendruscolo, Michele
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2015-01
Volume
427
Issue
2
Pages
478-490
ISSN
0022-2836 (ISSN-L)
OpenAlex
W2103083136
Cited by
494
References
62
Citations by year
2026: 52 · 2025: 77 · 2024: 60 · 2023: 42 · 2022: 62 · 2021: 59 · 2020: 44 · 2019: 33 · 2018: 28 · 2017: 20 · 2016: 9 · 2015: 7
FWCI
4.92
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
protein solubility, rational protein design, site-directed mutagenesis, nanobodies, amyloid-beta, Alzheimer's disease, soluble protein production, native state stability
MeSH terms
Amino Acids, Circular Dichroism, Cloning, Molecular, Computer Simulation, Escherichia coli, Models, Molecular, Protein Conformation, Recombinant Proteins, Solubility, Protein Engineering, Molecular Structure, Mutant Proteins, Chemical Phenomena

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