Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Proteins undergo dynamic interactions with carbohydrates, lipids and nucleotides to form catalytic cores, fine-tuned for different cellular actions. The study of dynamic interactions between proteins and their cognate ligands is therefore fundamental to the understanding of biological systems. During the last two decades MS, and its associated techniques, has become accepted as a method for the study of protein-ligand interactions, not only for covalent complexes, where the use of MS is well established, but also, and significantly for protein-ligand interactions, for noncovalent assemblies. In this review, we employ a broad definition of a ligand to encompass protein subunits, drug molecules, oligonucleotides, carbohydrates, and lipids. Under the appropriate conditions, MS can reveal the composition, heterogeneity and dynamics of these protein-ligand interactions, and in some cases their structural arrangements and binding affinities. Herein, we highlight MS approaches for studying protein-ligand complexes, including those containing integral membrane subunits, and showcase examples from recent literature. Specifically, we tabulate the myriad of methodologies, including hydrogen exchange, proteomics, hydroxyl radical footprinting, intact complexes, and crosslinking, which, when combined with MS, provide insights into conformational changes and subtle modifications in response to ligand-binding interactions.

Original publication




Journal article



Publication Date





1950 - 1964


MS, crosslinking, hydrogen-deuterium exchange, hydroxyl radical footprinting, protein complexes, protein-ligand interactions, proteomics, Humans, Hydroxyl Radical, Mass Spectrometry, Models, Biological, Proteins, Proteomics