Computational prediction and redesign of aberrant protein oligomerization

Jaime Santos*, Valentín Iglesias, Salvador Ventura

*Corresponding author for this work

Research output: Chapter in BookChapterResearchpeer-review

9 Citations (Scopus)


Non-native intermolecular contacts often lead to aberrant protein oligomerization and aggregation. This phenomenon is behind the onset of several human disorders and is a bottleneck for the production of proteins of biotechnological interest. Intrinsically disordered proteins have evolved to avoid aberrant oligomerization, but mutations or aging-promoted degeneration of the protein quality machinery might result in their aggregation. Folded globular proteins are not completely protected from aggregation, mostly because the physicochemical properties stabilizing their tertiary and/or quaternary structures are very similar to those leading to non-native oligomerization. Once these properties are known, it becomes feasible to predict the aggregation propensities of proteins and to design them to disfavor aggregation-prone contacts. In this chapter, we describe how computational approaches can assist the identification of the aggregation-prone sequential or structural regions leading to aberrant oligomerization and how these tools can be employed to predict pathogenic mutations or to design biotherapeutics with optimized solubility.

Original languageEnglish
Title of host publicationOligomerization in Health and Disease
Subtitle of host publicationFrom Enzymes to G Protein-Coupled Receptors
EditorsJesús Giraldo, Francisco Ciruela
Number of pages41
Publication statusPublished - 2020

Publication series

NameProgress in Molecular Biology and Translational Science
ISSN (Print)1877-1173
ISSN (Electronic)1878-0814


  • Amyloids
  • Bioinformatics
  • Conformational disorders
  • Evolution
  • Protein aggregation
  • Protein production


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