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G.G. Tartaglia; A. Cavalli; R. Pellarin; A. Caflisch

Journal: Protein Sci.
Year: 2005
Volume: 14
Issue: 10
Pages: 2723-2734
DOI: 10.1110/ps.051471205
Type of Publication: Journal Article

Alzheimer 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.