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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Nanoparticles*/chemistry ; Proteins*/genetics; Biocompatible Materials ; Decision Making ; Humans ; Peptides ; Protein Engineering/methods

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.

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R01 GM129325 United States GM NIGMS NIH HHS

Keywords: mutagenesis; nanomaterials; nanomedicine; protein stability

0 (Biocompatible Materials)
0 (Peptides)
0 (Proteins)

Date Created: 20220514 Date Completed: 20220517 Latest Revision: 20240923

20250114

PMC9099527

10.3390/ijms23094958

35563346