Protocols for Rational Design of Protein Solubility and Aggregation Properties Using Aggrescan3D Standalone

Aleksander Kuriata, Aleksandra E. Badaczewska-Dawid, Jordi Pujols, Salvador Ventura, Sebastian Kmiecik*

*Corresponding author for this work

Research output: Chapter in BookChapterResearchpeer-review

Abstract

Protein aggregation is a major hurdle in the development and manufacturing of protein-based therapeutics. Development of aggregation-resistant and stable protein variants can be guided by rational redesign using computational tools. Here, we describe the architecture and functionalities of the Aggrescan3D (A3D) standalone package for the rational design of protein solubility and aggregation properties based on three-dimensional protein structures. We present the case studies of the three therapeutic proteins, including antibodies, exploring the practical use of the A3D standalone tool. The case studies demonstrate that protein solubility can be easily improved by the A3D prediction of non-destabilizing amino acid mutations at the protein surfaces.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
Pages17-40
Number of pages24
DOIs
Publication statusPublished - 2022

Publication series

NameMethods in Molecular Biology
Volume2340
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Aggregation prediction
  • Aggrescan3D
  • Computational modeling
  • Protein aggregation
  • Protein design
  • Structure-based design

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