Applying mass spectrometry tools to investigate protein-protein and protein-ligand interactions.

Proteins do not function alone and interact with other partners within cells to carry out their function. Alterations in these protein interactions can change cellular function resulting in disease. This project has used mass spectrometry as a tool to monitor how protein interactions are changing upon adding a variety of biological molecules to them. The project has had a strong focus on molecular glues. These are therapeutically fascinating molecules that 'glue' proteins together that have fallen apart in cells due to a variety of environmental factors. We can also use molecular glues to deliberately force proteins to interact with one another, changing the balance of protein interactions within a cell. Monitoring whether these glues are working or not, has been extremely challenging as all the individual parts need to be detected at the same time as the 'glued' product. This has hindered molecular glue discovery. Mass spectrometry can monitor glues extremely effectively, since it has the capability to discriminate between all components in a mixture based of their differences in mass. This project has demonstrated the benefits of mass spectrometry within the molecular glue industry, revealing details of how good a 'glue' is at fixing specific protein-protein interactions but also in revealing insights into how serendipitously discovered 'glues' work.