#FragLites offer a fast, chemically rich method to identify allosteric sites, guide probe development, and validate AI-generated structural models. Their ability to mimic key interaction residues makes them ideal for designing separation-of-function mutations and selective inhibitors. 🧵3/3

While FragLites reliably bound to established interaction regions like the Palm site, ATP cleft, and RXL motif, we see a previously uncharacterized site at the CDK2–cyclin A interface. This site, rich in fragment engagement, may extend the SKP2 binding surface described by Kelso et al. (2021). 🧵 2/3

Crystallography for the "dark proteome"? From @nudrugdiscovery.bsky.social and @chemistryncl.bsky.social : #FragLites map protein–protein interaction sites including regions with no previously known function. 🧵1/3 #DrugDiscovery #ChemBio
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Looking forward to speaking at this on Tuesday. Apparently they are keen to hear about #fraglites and #dels - we will see www.nepic.co.uk/event/nepic-...

Preprint out now! We used FragLites to map a complex for which there are structurally characterised partner proteins and show how the FragLites are really good at (a) preferentially binding to PPI sites, and (b) mimicking hotspot interactions. This can help guide separation-of-function mutations!

Crystallographic fragment screening of CDK2-cyclin A: FragLites map sites of protein-protein interaction https://www.biorxiv.org/content/10.1101/2024.06.03.596235v1

Crystallographic fragment screening of CDK2-cyclin A: FragLites map sites of protein-protein interaction https://www.biorxiv.org/content/10.1101/2024.06.03.596235v1