Cited by 494Protein Structure and DynamicsProtein purification and stabilityEnzyme Structure and Function

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The CamSol Method of Rational Design of Protein Mutants with Enhanced Solubility

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

DOI 10.1016/j.jmb.2014.09.026

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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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“6 47,48 (Supplementary Fig.”
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“Next, we added a solubility ﬁ lter using the structurally-corrected version of CamSol (Sormanni et al, 2015), a computational method to identify regions of low solubility on the surfaces of protein structures (Fig.”
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“…(accessed on 23 May 2024)), Solubis [14] (https://solubis.switchlab.org/ ( accessed on 23 May 2024)), or Camsol [15] (https://www-cohsoftware.ch.cam.ac.uk (accessed on 23 May 2024)) use bioinformatics-based methods instead of MD-based methods (for a collection…”
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Modifying recombinant purple acid phosphatase using computational design
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“Previous studies have demonstrated that a combination of mutations are often necessary to achieve substantial improvements in protein stability and solubility (Sormanni et al. 2015; Bhadouria et al. 2017; Bhadouria and Giri 2022).”
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“46 The resulting prediction was encoded into the B-factor of the protein and visualized with PyMol.”
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MethodSelf-citation
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Method
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“Focusing on the membrane receptors solubilized by SMA, we analysed the amino acid sequence properties of identified proteins and calculated an overall solubility score (Sormanni et al., 2015; Sormanni et al., 2017).”
Method
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“The calculation of the overall solubility, performed as described in (26), on the WT form and the two mutant variants (Table S3) demonstrates how solubility of both mutants has also increased compared to that of the WT form.”
Method
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“The CamSol method [36] was used via the online server (https://www-629 cohsoftware.ch.cam.ac.uk/index.php/camsolcombination) to propose solubility-improving mutations for the 19 αBgtx poly-specific V H Hs with high-confidence structures.”
Influential
ATM kinase phosphorylates Ser15 of p53 in a pH-dependent manner
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Heterologous Production and Characterization of Rapeseed Procruciferin Isoforms for Sustainable Food Protein Development
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Self-citation

Authors: Sormanni, P., Aprile, F. A., & Vendruscolo, M.
Affiliations: University of Cambridge (GB)
Corresponding author: Vendruscolo, Michele
ORCID: Sormanni, Pietro
Aprile, Francesco A.
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)
DOI: 10.1016/j.jmb.2014.09.026
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › 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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The CamSol Method of Rational Design of Protein Mutants with Enhanced Solubility

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