An In Silico Methodology That Facilitates Decision Making in the Engineering of Nanoscale Protein Materials

Eloi Parladé*, Eric Voltà-Durán, Olivia Cano-Garrido, Julieta M. Sánchez, Ugutz Unzueta, Hèctor López-Laguna, Naroa Serna, Montserrat Cano, Manuel Rodríguez-Mariscal, Esther Vazquez, Antonio Villaverde*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)


Under the need for new functional and biocompatible materials for biomedical applications, protein engineering allows the design of assemblable polypeptides, which, as convenient building blocks of supramolecular complexes, can be produced in recombinant cells by simple and scalable methodologies. However, the stability of such materials is often overlooked or disregarded, becoming a potential bottleneck in the development and viability of novel products. In this context, we propose a design strategy based on in silico tools to detect instability areas in protein materials and to facilitate the decision making in the rational mutagenesis aimed to increase their stability and solubility. As a case study, we demonstrate the potential of this methodology to improve the stability of a humanized scaffold protein (a domain of the human nidogen), with the ability to oligomerize into regular nanoparticles usable to deliver payload drugs to tumor cells. Several nidogen mutants suggested by the method showed important and measurable improvements in their structural stability while retaining the functionalities and production yields of the original protein. Then, we propose the procedure developed here as a cost-effective routine tool in the design and optimization of multimeric protein materials prior to any experimental testing.

Original languageEnglish
Article number4958
Number of pages12
JournalInternational journal of molecular sciences
Issue number9
Publication statusPublished - 1 May 2022


  • mutagenesis
  • nanomaterials
  • nanomedicine
  • protein stability


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