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. 2013;8(1):e54175.
doi: 10.1371/journal.pone.0054175. Epub 2013 Jan 10.

A Consensus Method for the Prediction of 'Aggregation-Prone' Peptides in Globular Proteins

Free PMC article

A Consensus Method for the Prediction of 'Aggregation-Prone' Peptides in Globular Proteins

Antonios C Tsolis et al. PLoS One. .
Free PMC article


The purpose of this work was to construct a consensus prediction algorithm of 'aggregation-prone' peptides in globular proteins, combining existing tools. This allows comparison of the different algorithms and the production of more objective and accurate results. Eleven (11) individual methods are combined and produce AMYLPRED2, a publicly, freely available web tool to academic users (, for the consensus prediction of amyloidogenic determinants/'aggregation-prone' peptides in proteins, from sequence alone. The performance of AMYLPRED2 indicates that it functions better than individual aggregation-prediction algorithms, as perhaps expected. AMYLPRED2 is a useful tool for identifying amyloid-forming regions in proteins that are associated with several conformational diseases, called amyloidoses, such as Altzheimer's, Parkinson's, prion diseases and type II diabetes. It may also be useful for understanding the properties of protein folding and misfolding and for helping to the control of protein aggregation/solubility in biotechnology (recombinant proteins forming bacterial inclusion bodies) and biotherapeutics (monoclonal antibodies and biopharmaceutical proteins).

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Figure 1
Figure 1. The crystal structure (space-filling model) of the anti-ErbB2 Fab2C4 (PDB code: 1L7I) is shown.
(A). This is a humanized monoclonal antibody fragment that binds to the extracellular domain of the human oncogene product ErbB2 (ErbB2 has been shown to play an important role in the pathogenesis of certain aggressive types of breast cancer). Computationally predicted ‘aggregation-prone’ regions by AMYLPRED2 are coloured red. Performing only two single amino acid substitutions (T28G and I201E), the AMYLPRED2 output suggests that the antibody has ‘lost’ two crucial ‘aggregation-prone’ regions and may, therefore, be more soluble, not forming aggregates (B). Molecular graphics were performed with the UCSF Chimera package. Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS 9P41GM103311) .

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Grant support

The authors thank the University of Athens for support. They also thank the Cooperation 2011 program (11SYN_1_1230) of the General Secretariat for Research and Technology of the Greek Ministry of Education and Religious Affairs, Culture and Sports, under the NSRF 2007–2013, for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.