Crosslinking mass spectrometry has become a core technology in structural biology and is expanding its reach towards systems biology. Its appeal lies in a rapid workflow, high sensitivity and the ability to provide data on proteins in complex systems, even in whole cells. The technology depends heavily on crosslinking reagents. The anatomy of crosslinkers can be modular, sometimes comprising combinations of functional groups. These groups are defined by concepts including: reaction selectivity to increase information density, enrichability to improve detection, cleavability to enhance the identification process and isotope-labelling for quantification. Here, we argue that both concepts and functional groups need more thorough experimental evaluation, so that we can show exactly how and where they are useful when applied to crosslinkers. Crosslinker design should be driven by data, not only concepts. We focus on two crosslinker concepts with large consequences for the technology, namely reactive group reaction kinetics and enrichment groups.

中文翻译：

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交联剂的解剖。

交联质谱已成为结构生物学的核心技术，并正在将其范围扩展到系统生物学。它的吸引力在于快速的工作流程、高灵敏度以及提供复杂系统（甚至整个细胞）中蛋白质数据的能力。该技术在很大程度上依赖于交联剂。交联剂的解剖结构可以是模块化的，有时包括功能组的组合。这些组由概念定义，包括：增加信息密度的反应选择性、改进检测的富集性、增强识别过程的可裂解性和用于定量的同位素标记。在这里，我们认为概念和官能团都需要更彻底的实验评估，以便我们可以准确地展示它们在应用于交联剂时如何以及在何处有用。交联剂设计应该由数据驱动，而不仅仅是概念。我们专注于对技术产生重大影响的两个交联剂概念，即反应性基团反应动力学和富集基团。