AGGRESCAN3D (A3D): Server for prediction of aggregation properties of protein structures

Rafael Zambrano, Michal Jamroz, Agata Szczasiuk, Jordi Pujols, Sebastian Kmiecik, Salvador Ventura

Research output: Contribution to journalArticleResearchpeer-review

111 Citations (Scopus)

Abstract

© 2015 The Author(s). Protein aggregation underlies an increasing number of disorders and constitutes a major bottleneck in the development of therapeutic proteins. Our present understanding on themolecular determinants of protein aggregation has crystalized in a series of predictive algorithms to identify aggregation-prone sites. A majority of these methods rely only on sequence. Therefore, they find difficulties to predict the aggregation properties of folded globular proteins, where aggregation-prone sites are often not contiguous in sequence or buried inside the native structure. The AGGRESCAN3D (A3D) server overcomes these limitations by taking into account the protein structure and the experimental aggregation propensity scale from the well-established AGGRESCAN method. Using the A3D server, the identified aggregation-prone residues can be virtually mutated to design variants with increased solubility, or to test the impact of pathogenic mutations. Additionally, A3D server enables to take into account the dynamic fluctuations of protein structure in solution, which may influence aggregation propensity. This is possible in A3D Dynamic Mode that exploits the CABS-flex approach for the fast simulations of flexibility of globular proteins. The A3D server can be accessed at http://biocomp.chem.uw.edu.pl/A3D/.
Original languageEnglish
Pages (from-to)W306-W313
JournalNucleic Acids Research
Volume43
Issue numberW1
DOIs
Publication statusPublished - 1 Jan 2015

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