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. 2025 Jul 7;53(W1):W463-W465.
doi: 10.1093/nar/gkaf361.

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

Affiliations

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

Philipp Schake et al. Nucleic Acids Res. .

Abstract

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.

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Conflict of interest statement

None declared.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Bcl-2 interacting with the BAX protein and the small molecule venetoclax. (A, B) Surface view showing that BAX and venetoclax bind at the same binding site. (C, D) PLIP interactions for BAX/Bcl-2 and venetoclax reveal the key interacting residues of Bcl-2, a common hydrogen bond network of Bcl-2 residues N143, W144, and G145, and shared hydrophobic contacts with Bcl-2 residues F104, Y108, and F153.

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