An In Silico Methodology That Facilitates Decision Making in the Engineering of Nanoscale Protein Materials
Parladé Molist, Eloi (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Voltà-Durán, Eric (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Cano-Garrido, Olivia (Universitat Autònoma de Barcelona. Nanoligent S.L)
Sanchez, Julieta M. (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Unzueta Elorza, Ugutz (Institut d'Investigació Biomèdica Sant Pau)
López-Laguna, Hèctor (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Serna, Naroa (Universitat Autònoma de Barcelona. Nanoligent S.L)
Cano, Montserrat (Universitat Autònoma de Barcelona. Nanoligent S.L)
Rodríguez-Mariscal, Manuel (Universitat Autònoma de Barcelona. Nanoligent S.L)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date:	2022
Abstract:	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.
Grants:	Ministerio de Ciencia e Innovación RTC-2017-6125-1 Agència de Gestió d'Ajuts Universitaris i de Recerca 2019/FI_B00352 Ministerio de Ciencia e Innovación FPU18/04615 Instituto de Salud Carlos III CP19/00028
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; Versió publicada
Subject:	Nanomaterials ; Protein stability ; Nanomedicine ; Mutagenesis
Published in:	International journal of molecular sciences, Vol. 23, Issue 9 (May 2022) , art. 4958, ISSN 1422-0067

DOI: 10.3390/ijms23094958
PMID: 35563346

12 p, 2.9 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Published articles