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Prediction of aggregation rate and aggregation‐prone segments in polypeptide sequences
Author(s) -
Tartaglia Gian Gaetano,
Cavalli Andrea,
Pellarin Riccardo,
Caflisch Amedeo
Publication year - 2005
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.051471205
Subject(s) - protein aggregation , computational biology , beta (programming language) , human proteins , peptide , prion protein , chemistry , fibril , sequence (biology) , biophysics , biology , biochemistry , disease , computer science , gene , medicine , pathology , programming language
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.