Prediction of aggregation rate and aggregation-prone segments in polypeptide sequences

TitlePrediction of aggregation rate and aggregation-prone segments in polypeptide sequences
Publication TypeJournal Article
Year of Publication2005
AuthorsTartaglia G.G, Cavalli A., Pellarin R., Caflisch A.
JournalProtein Science
Date Published2005 Oct
Type of ArticleResearch Article
KeywordsAlzheimer Disease, Amino Acid Sequence, Amyloid, Drug Design, Humans, Models, Chemical, Parkinson Disease, Prions, Protein Denaturation, Protein Structure, Secondary

The reliable identification of β-aggregating stretches in protein sequences is essential for the development of therapeutic agents for Alzheimer's and Parkinson's diseases, as well as other pathological conditions associated with protein deposition. Here, a model based on physicochemical properties and computational design of β-aggregating peptide sequences is shown to be able to predict the aggregation rate over a large set of natural polypeptide sequences. Furthermore, the model identifies aggregation-prone fragments within proteins and predicts the parallel or anti-parallel β-sheet organization in fibrils. The model recognizes different β-aggregating segments in mammalian and nonmammalian prion proteins, providing insights into the species barrier for the transmission of the prion disease.



Alternate JournalProtein Sci.
PubMed ID16195556
PubMed Central IDPMC2253302
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