The cellular thermal shift assay (CETSA) is a biophysical technique allowing direct studies of ligand binding to proteins in cells and tissues. The proteome-wide implementation of CETSA with mass spectrometry detection (MS-CETSA) has now been successfully applied to discover targets for orphan clinical drugs and hits from phenotypic screens, to identify off-targets, and to explain poly-pharmacology and drug toxicity. Highly sensitive multidimensional MS-CETSA implementations can now also access binding of physiological ligands to proteins, such as metabolites, nucleic acids, and other proteins. MS-CETSA can thereby provide comprehensive information on modulations of protein interaction states in cellular processes, including downstream effects of drugs and transitions between different physiological cell states. Such horizontal information on ligandmodulation in cells is largely orthogonal to vertical information on the levels of different proteins and therefore opens novel opportunities to understand operational aspects of cellular proteomes.

中文翻译：

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水平细胞生物学：用蛋白质组学范围的细胞热位移分析（CETSA）监测蛋白质相互作用状态的整体变化。

细胞热位移分析（CETSA）是一种生物物理技术，可以直接研究配体与细胞和组织中蛋白质的结合。CETSA在蛋白质组学范围内的质谱检测（MS-CETSA）实施现已成功应用于发现孤儿临床药物的靶标和来自表型筛选的命中物，以识别靶标以外的靶标，并解释多药理学和药物毒性。高敏感性多维MS-CETSA实现现在还可以访问生理配体与蛋白质（例如代谢产物，核酸和其他蛋白质）的结合。因此，MS-CETSA可以提供有关细胞过程中蛋白质相互作用状态调节的全面信息，包括药物的下游效应以及不同生理细胞状态之间的转变。