Protein Dynamics in Solution by Quantitative Crosslinking/Mass Spectrometry

The dynamics of protein structures and their interactions are responsible for many cellular processes. The rearrangements and interactions of proteins, which are often transient, occur in solution and may require a biological environment that is difficult to maintain in traditional structural biological approaches. Quantitative crosslinking/mass spectrometry (QCLMS) has emerged as an excellent method to fill this gap. Numerous recent applications of the technique have demonstrated that protein dynamics can now be studied in solution at sufficient resolution to gain valuable biological insights, suggesting that extending these investigations to native environments is possible. These breakthroughs have been based on the maturation of CLMS at large, and its recent fusion with quantitative proteomics. We provide here an overview of the current state of the technique, the available workflows and their applications, and remaining challenges.