PLIP 2025: introducing protein–protein interactions to the protein–ligand interaction profiler

PLIP, the protein-ligand interaction profiler, analyses molecular interactions in protein structures. PLIP detects eight types of non-covalent interactions. Initially focused on small-molecule, DNA, and RNA interactions to a protein, the current release incorporates protein-protein interactions. We document the usefulness of this feature by comparing PLIP interactions of the cancer drug venetoclax with the native protein-protein interaction of Bcl-2 and BAX. PLIP reveals how the drug mimics the native interaction, as there is critical overlap in the interaction profiles. PLIP is available as a web server, source code with containers, and Jupyter notebook. The PLIP web server is online at https://plip-tool.biotec.tu-dresden.de.