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
Volume14
Issue10
Pagination2723-2734
Date Published2005 Oct
Type of ArticleResearch Article
ISSN0961-8368
KeywordsAlzheimer Disease, Amino Acid Sequence, Amyloid, Drug Design, Humans, Models, Chemical, Parkinson Disease, Prions, Protein Denaturation, Protein Structure, Secondary
Abstract

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.

DOI10.1110/ps.051471205
pubindex

0069

Alternate JournalProtein Sci.
PubMed ID16195556
PubMed Central IDPMC2253302
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