Capturing the dynamic interplay between proteins and their myriad interaction partners is critically important for advancing our understanding of almost every biochemical process and human disease. The importance of this general area has spawned many measurement methods capable of assaying such protein complexes, and the mass spectrometry–based structural biology methods described in this review form an important part of that analytical arsenal. Here, we survey the basic principles of such measurements, cover recent applications of the technology that have focused on protein–small-molecule complexes, and discuss the bright future awaiting this group of technologies.

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