title: Prediction of aggregation rate and aggregation-prone segments in polypeptide sequences.
abstract: The reliable identification of beta-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 beta-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 beta-sheet organization in fibrils. The model recognizes different beta-aggregating segments in mammalian and nonmammalian prion proteins, providing insights into the species barrier for the transmission of the prion disease.
authors.affiliation: Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Gian Gaetano
authors.initials: GG
authors.lastname: Tartaglia
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pellarin
authors.forename: Amedeo
authors.initials: A
authors.lastname: Caflisch
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D011328:Prions / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D011328:Prions