Prediction of aggregation rate and aggregation‐prone segments in polypeptide sequences
- 1 October 2005
- journal article
- Published by Wiley in Protein Science
- Vol. 14 (10) , 2723-2734
- https://doi.org/10.1110/ps.051471205
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.Keywords
This publication has 80 references indexed in Scilit:
- Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteinsNature Biotechnology, 2004
- A Comparative Study of the Relationship Between Protein Structure and β-Aggregation in Globular and Intrinsically Disordered ProteinsJournal of Molecular Biology, 2004
- Prediction of the Absolute Aggregation Rates of Amyloidogenic Polypeptide ChainsJournal of Molecular Biology, 2004
- Mapping Aβ Amyloid Fibril Secondary Structure Using Scanning Proline MutagenesisJournal of Molecular Biology, 2004
- Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolutionJournal of Molecular Medicine, 2003
- Rationalization of the effects of mutations on peptide andprotein aggregation ratesNature, 2003
- CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choiceNucleic Acids Research, 1994
- The N-terminal segment of protein AA determines its fibrillogenic propertyBiochemical and Biophysical Research Communications, 1992
- Variant apolipoprotein AI as a major constituent of a human hereditary amyloidBiochemical and Biophysical Research Communications, 1988
- CHARMM: A program for macromolecular energy, minimization, and dynamics calculationsJournal of Computational Chemistry, 1983