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Computational optimization of DEK1 calpain domain solubility through integrated structural modelling and data-driven targeted mutagenesis

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Dabiri, Mohammad, Levarski, Zdenko, Struhárňanská, Eva, Demko, Viktor, Beneš, Vladimir, Turňa, Jan, Stuchlík, Stanislav·2026·Scientific Reports
DOI 10.1038/s41598-026-38805-zPMC PMC12948991

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Abstract

The DEFECTIVE KERNEL 1 (DEK1) protein plays essential functions throughout plant development. DEK1 is a multidomain 240 kDa protein with yet unsolved 3D structure. To facilitate structural and functional studies of DEK1, here we investigate its calpain protease core domain (CysPc) from Physcomitrium patens. Using integrated structural modelling we propose targeted mutagenesis of CysPc to enhance its solubility during recombinant protein production. We created a pipeline to predict the topology of the CysPc domain with improved precision, providing a robust framework for further exploration. We evaluated the native and mutant structures by MD simulations, concentrating on several solubility-related parameters. Following these features, we implemented specific single, double, and triple amino acid mutagenesis to select variants with improved solubility. Our method preserves overall structural integrity while reducing aggregation-prone traits. We advocate for the utilization of optimized data driven method that can effectively traverse the extensive combinatorial space and prioritize mutation sets with the greatest potential for enhancing solubility. This framework provides a logical, data-driven approach to improving protein solubility, particularly beneficial in situations lacking high-resolution structural data.

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Metadata

Authors
Dabiri, M., Levarski, Z., Struhárňanská, E., Demko, V., Beneš, V., Turňa, J., & Stuchlík, S.
Affiliations
  • Comenius University Bratislava (SK)
  • Slovak Academy of Sciences (SK)
Corresponding author
  • Dabiri, Mohammad
  • Levarski, Zdenko
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2026-02-08
Volume
16
Issue
1
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-026-38805-z
PMC
PMC12948991
OpenAlex
W7128355779
Cited by
0
References
6
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Fostering Excellence in Advanced Genomics and Proteomics Research at Comenius University in Bratislava (FORGENOM II, APVV-21-0227, APVV-21-0215, APVV-22-0161 , 101160008)
  • Univerzita Komenského v Bratislave CU Grant 2025 (UK/1088/2025)
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, targeted mutagenesis, protein aggregation, Physcomitrella patens, protein topology prediction, molecular dynamics simulation, recombinant protein expression, protein structure prediction, computational protein design
MeSH terms
Protein Domains, Calpain, Models, Molecular, Mutation, Plant Proteins, Solubility, Mutagenesis, Bryopsida, Molecular Dynamics Simulation

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