Probabilistic enrichment of phosphopeptides by their mass defect
Probabilistic enrichment of phosphopeptides by their mass defect
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DOI：
10.1021/ac060046w
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发表时间：
2006-07-01
影响因子：
7.4
通讯作者：
Gulcicek, Erol E.
中科院分区：
文献类型：
--
作者：
Bruce, Can;Shifman, Mark A.;Gulcicek, Erol E.
磷的质量缺陷，即名义质量和实际单同位素质量之间的差异，比蛋白质中存在的大多数其他原子都要大。当从人类蛋白质组中提取的色氨酸肽的质量缺陷与它们的质量进行对比时，磷酸肽倾向于偏离回归线。通过计算人类蛋白质组中所有潜在的色氨酸肽的质量，我们表明在这样的图上存在较高的磷酸化概率区域。我们开发了一个转换函数，用于从单同位素质量估计肽的质量缺陷，并根据经验定义了一个简单的公式，用于用户可选择的判别线，根据其被磷酸化的概率对肽质量进行分类。我们的方法对从实验验证的磷酸化蛋白数据库中获得的磷酸肽也有类似的效果。该方法对高达20ppm的质量测量误差相对不敏感。该方法可以与串联质谱实时使用，从未修饰的肽混合物中快速选择和排序可能的磷酸肽，用于随后的磷酸化位点定位和肽序列分析。
The mass defect, that is, the difference between the nominal and actual monoisotopic masses, of a phosphorus in a phosphate group is greater than for most other atoms present in proteins. When the mass defects of tryptic peptides derived from the human proteome are plotted against their masses, phosphopeptides tend to fall off the regression line. By calculating the masses of all potential tryptic peptides from the human proteome, we show that regions of higher phosphorylation probability exist on such a plot. We developed a transformation function to estimate the mass defect of a peptide from its monoisotopic mass and empirically defined a simple formula for a user-selectable discriminant line that categorizes a peptide mass according to its probability of being phosphorylated. Our method performs similarly well on phosphopeptides derived from a database of experimentally validated phosphoproteins. The method is relatively insensitive to mass measurement error of up to 20 ppm. The approach can be used with a tandem mass spectrometer in real time to rapidly select and rank order the possible phosphopeptides from a mixture of unmodified peptides for subsequent phosphorylation site mapping and peptide sequence analysis.