Chemical proteomics for a comprehensive understanding of functional activity and the interactome

초록

Traditional mass spectrometry (MS)-based proteomics aims to detect and measure protein expression on a global scale and elucidate the link between protein function and phenotypic characteristics. Although advances in MS technology have significantly broadened the scope of detectable proteomes, these methodologies primarily provide data on protein abundance and offer limited insights into their functional activities. Phenotypic traits emerge from the interplay between protein abundance and functional activity, making the accurate measurement of activity a critical but challenging task, owing to the complexity of biological systems. Furthermore, the biological function of a protein is strongly linked to its interaction with other molecules within the cellular environment. Chemical proteomics offers a complementary approach that uses a toolkit developed in chemical biology to map the molecular interactome and provide initial insights into the activities of specific target proteins. However, the value of these techniques lies not in isolation, but as part of a broader experimental workflow that includes follow-up biological investigations to validate the findings and elucidate their functional relevance. This tutorial review highlights the design principles of chemical tools and examines their applications in two key areas: (i) functional activity profiling of biomolecules and (ii) molecular proximity profiling for interactome characterization. We also discuss the importance of the experimental context in shaping data interpretation and ensuring the practical adoption of these methods by biologists. Although chemical proteomics is not a standalone solution, it represents a promising step toward next-generation omics technologies and advances our understanding of biological functions at the molecular level.

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