Targeting membrane proteins at sites embedded in the lipid bilayer offers the potential to discover ligands for undruggable targets; however, ligand binding at the protein-membrane interface remains underexplored. Here, the authors introduce the Lipid-Interacting LigAnd Complexes Database (LILAC-DB), a curated dataset of 413 structures of ligands bound at the protein-bilayer interface, identifying that lipid-exposed small molecules have distinct chemical properties that depend on their position in the bilayer and demonstrating the distinct amino acid compositions of these lipid-exposed binding sites.
- Allison Pearl Barkdull
- Matthew Holcomb
- Stefano Forli
