Identification of 14-3-3 Proteins Phosphopeptide-Binding Specificity Using an Affinity-Based Computational Approach
| Autor: | Fei Guo, Zhao Li, Jijun Tang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Proteomics
Phosphopeptides 0301 basic medicine Amino Acid Motifs lcsh:Medicine Peptide Protein Sequencing Plasma protein binding Biochemistry Physical Chemistry Chromatography Affinity Mathematical and Statistical Techniques 0302 clinical medicine Protein sequencing Protein Isoforms Amino Acids Peptide Libraries lcsh:Science Peptide sequence chemistry.chemical_classification Crystallography Multidisciplinary Covariance Phosphopeptide Physics Condensed Matter Physics Amino acid Chemistry Physicochemical Properties 030220 oncology & carcinogenesis Physical Sciences Crystal Structure Regression Analysis Sequence Analysis Statistics (Mathematics) Research Article Protein Binding Gene isoform Molecular Sequence Data Linear Regression Analysis Biology Research and Analysis Methods 03 medical and health sciences Sequence Motif Analysis Solid State Physics Humans Position-Specific Scoring Matrices Amino Acid Sequence Statistical Methods Molecular Biology Techniques Sequencing Techniques Molecular Biology Binding selectivity lcsh:R Biology and Life Sciences Computational Biology Reproducibility of Results Random Variables Probability Theory Physical Properties 030104 developmental biology Chemical Properties 14-3-3 Proteins chemistry lcsh:Q Peptides Mathematics |
| Zdroj: | PLoS ONE, Vol 11, Iss 2, p e0147467 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The 14-3-3 proteins are a highly conserved family of homodimeric and heterodimeric molecules, expressed in all eukaryotic cells. In human cells, this family consists of seven distinct but highly homologous 14-3-3 isoforms. 14-3-3σ is the only isoform directly linked to cancer in epithelial cells, which is regulated by major tumor suppressor genes. For each 14-3-3 isoform, we have 1,000 peptide motifs with experimental binding affinity values. In this paper, we present a novel method for identifying peptide motifs binding to 14-3-3σ isoform. First, we propose a sampling criteria to build a predictor for each new peptide sequence. Then, we select nine physicochemical properties of amino acids to describe each peptide motif. We also use auto-cross covariance to extract correlative properties of amino acids in any two positions. Finally, we consider elastic net to predict affinity values of peptide motifs, based on ridge regression and least absolute shrinkage and selection operator (LASSO). Our method tests on the 1,000 known peptide motifs binding to seven 14-3-3 isoforms. On the 14-3-3σ isoform, our method has overall pearson-product-moment correlation coefficient (PCC) and root mean squared error (RMSE) values of 0.84 and 252.31 for N-terminal sublibrary, and 0.77 and 269.13 for C-terminal sublibrary. We predict affinity values of 16,000 peptide sequences and relative binding ability across six permutated positions similar with experimental values. We identify phosphopeptides that preferentially bind to 14-3-3σ over other isoforms. Several positions on peptide motifs are in the same amino acid category with experimental substrate specificity of phosphopeptides binding to 14-3-3σ. Our method is fast and reliable and is a general computational method that can be used in peptide-protein binding identification in proteomics research. |
| Databáze: | OpenAIRE |
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