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 GG, Cavalli A, Pellarin R, Caflisch A
JournalProtein Sci.
Volume14
Pagination2723–2734
Date PublishedOct
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.

URLhttp://dx.doi.org/10.1110/ps.051471205
DOI10.1110/ps.051471205