Prediction of aggregation rate and aggregation-prone segments in polypeptide sequences

被引：171

作者：

Tartaglia, GG ^{[1
]}

Cavalli, A ^{[1
]}

Pellarin, R ^{[1
]}

Caflisch, A ^{[1
]}

机构：

[1] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland

来源：

PROTEIN SCIENCE | 2005年 / 14卷 / 10期

关键词：

Alzheimer's disease; amyloid; protein aggregation rate; priori protein; species barrier; genetic algorithm; molecular dynamics;

D O I：

10.1110/ps.051471205

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 priori proteins, providing insights into the species barrier for the transmission of the priori disease.

引用

页码：2723 / 2734

页数：12

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