Prediction of aggregation rate and aggregation-prone segments in polypeptide sequences.
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.
Tartaglia
Gian Gaetano
GG
Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Cavalli
Andrea
A
Pellarin
Riccardo
R
Caflisch
Amedeo
A
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
D000682:Amyloid; D011328:Prions