cooperativity among short amyloid stretches in long amyloidogenic sequences协同在短淀粉样泡在长amyloidogenic序列.pdfVIP

Cooperativity among Short Amyloid Stretches in Long Amyloidogenic Sequences 1,3. 2. 2 4 5 6 1 Lele Hu , Weiren Cui , Zhisong He , Xiaohe Shi , Kaiyan Feng , Buyong Ma *, Yu-Dong Cai * 1 Institute of Systems Biology, Shanghai University, Shanghai, People’s Republic of China, 2 CAS-MPG Partner Institute of Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China, 3 Department of Chemistry, College of Sciences, Shanghai University, Shanghai, People’s Republic of China, 4 Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, 5 Shanghai Center for Bioinformation Technology, Shanghai, China, 6 Basic Science Program, SAIC – Frederick, Center for Cancer Research Nanobiology Program, National Cancer Institute-Fredeick, National Institute of Health, Frederick, Maryland, United States of America Abstract Amyloid fibrillar aggregates of polypeptides are associated with many neurodegenerative diseases. Short peptide segments in protein sequences may trigger aggregation. Identifying these stretches and examining their behavior in longer protein segments is critical for understanding these diseases and obtaining potential therapies. In this study, we combined machine learning and structure-based energy evaluation to examine and predict amyloidogenic segments. Our feature selection method discovered that windows consisting of long amino acid segments of ,30 residues, instead of the commonly used short hexapeptides, provided the highest accuracy. Weighted contributions of an amino acid at each position in a 27 residue windo