Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom.
Division of Molecular and Cellular Function, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom.
J Proteome Res. 2023 Feb 3;22(2):594-604. doi: 10.1021/acs.jproteome.2c00608. Epub 2023 Jan 23.
Protein quantitation via mass spectrometry relies on peptide proxies for the parent protein from which abundances are estimated. Owing to the variability in signal from individual peptides, accurate absolute quantitation usually relies on the addition of an external standard. Typically, this involves stable isotope-labeled peptides, delivered singly or as a concatenated recombinant protein. Consequently, the selection of the most appropriate surrogate peptides and the attendant design in recombinant proteins termed QconCATs are challenges for proteome science. QconCATs can now be built in a "a-la-carte" assembly method using synthetic biology: ALACATs. To assist their design, we present "AlacatDesigner", a tool that supports the peptide selection for recombinant protein standards based on the user's target protein. The user-customizable tool considers existing databases, occurrence in the literature, potential post-translational modifications, predicted miscleavage, predicted divergence of the peptide and protein quantifications, and ionization potential within the mass spectrometer. We show that peptide selections are enriched for good proteotypic and quantotypic candidates compared to empirical data. The software is freely available to use either via a web interface AlacatDesigner, downloaded as a Desktop application or imported as a Python package for the command line interface or in scripts.
通过质谱进行蛋白质定量依赖于肽段作为母蛋白的替代物来估计其丰度。由于来自单个肽段的信号存在可变性,因此准确的绝对定量通常依赖于外部标准的添加。通常,这涉及到稳定同位素标记的肽段,单独添加或作为串联重组蛋白添加。因此,选择最合适的替代肽段和随之而来的称为 QconCAT 的重组蛋白设计是蛋白质组学的挑战。现在可以使用合成生物学的“点菜式”组装方法构建 QconCAT:ALACATs。为了帮助设计,我们提供了“AlacatDesigner”,这是一种工具,它可以根据用户的目标蛋白来支持重组蛋白标准的肽段选择。用户可自定义的工具考虑了现有的数据库、文献中的出现情况、潜在的翻译后修饰、预测的错误切割、肽段和蛋白定量的预测差异以及质谱仪内的离子化势能。我们表明,与经验数据相比,肽段选择更丰富了良好的蛋白特征肽段和定量特征肽段候选物。该软件可通过网络界面 AlacatDesigner、下载为桌面应用程序或导入为命令行界面的 Python 包或脚本使用。