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A3D 2.0 Update for the Prediction and Optimization of Protein Solubility

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Insoluble Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2406))

Abstract

Protein aggregation propensity is a property imprinted in protein sequences and structures, being associated with the onset of human diseases and limiting the implementation of protein-based biotherapies. Computational approaches stand as cost-effective alternatives for reducing protein aggregation and increasing protein solubility. AGGRESCAN 3D (A3D) is a structure-based predictor of aggregation that takes into account the conformational context of a protein, aiming to identify aggregation-prone regions exposed in protein surfaces. Here we inspect the updated 2.0 version of the algorithm, which extends the application of A3D to previously inaccessible proteins and incorporates new modules to assist protein redesign. Among these features, the new server includes stability calculations and the possibility to optimize protein solubility using an experimentally validated computational pipeline. Finally, we employ defined examples to navigate the A3D RESTful service, a routine to handle extensive protein collections. Altogether, this chapter is conceived to train and assist A3D non-experts in the study of aggregation-prone regions and protein solubility redesign.

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Acknowledgments

This work was funded by the Spanish Ministry of Economy and Competitiveness BIO2016-78310-R to S.V and by ICREA, ICREA-Academia 2015 to S.V. J. S. and J.P. were supported by the Spanish Ministry of Science and Innovation via a doctoral grant (FPU17/01157 and FPU14/07161). Conflict of Interest: none declared

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Authors and Affiliations

  1. Institut de Biotecnologia i Biomedicina (IBB) and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barelona (UAB), Barcelona, Spain

    Jordi Pujols, Valentín Iglesias, Jaime Santos & Salvador Ventura

  2. Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Warsaw, Poland

    Aleksander Kuriata & Sebastian Kmiecik

Authors
  1. Jordi Pujols
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  2. Valentín Iglesias
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  3. Jaime Santos
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  4. Aleksander Kuriata
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  5. Sebastian Kmiecik
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  6. Salvador Ventura
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Corresponding author

Correspondence to Salvador Ventura .

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Editors and Affiliations

  1. Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Caldes de Montbui, Spain

    Elena Garcia Fruitós

  2. Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Caldes de Montbui, Spain

    Anna Arís Giralt

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Pujols, J., Iglesias, V., Santos, J., Kuriata, A., Kmiecik, S., Ventura, S. (2022). A3D 2.0 Update for the Prediction and Optimization of Protein Solubility. In: Garcia Fruitós, E., Arís Giralt, A. (eds) Insoluble Proteins. Methods in Molecular Biology, vol 2406. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1859-2_3

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  • DOI: https://doi.org/10.1007/978-1-0716-1859-2_3

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1858-5

  • Online ISBN: 978-1-0716-1859-2

  • eBook Packages: Springer Protocols

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