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PLIP 2025: introducing protein-protein interactions to the protein-ligand interaction profiler
Philipp Schake1, Sarah Naomi Bolz1, Katja Linnemann1
1Biotec and scads.ai, TU Dresden, 01307 Dresden, Germany.
Nucleic Acids Research
|May 10, 2025
Summary
The protein-ligand interaction profiler (PLIP) now analyzes protein-protein interactions, revealing how drugs like venetoclax mimic natural interactions by overlapping binding profiles.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Biology
Background:
- Protein structures contain complex molecular interactions crucial for biological functions.
- Understanding these interactions is key for drug discovery and development.
- The protein-ligand interaction profiler (PLIP) tool analyzes molecular interactions within protein structures.
Purpose of the Study:
- To introduce the enhanced PLIP tool capable of analyzing protein-protein interactions.
- To demonstrate the utility of PLIP in understanding drug mechanisms by comparing drug-target and native interactions.
- To provide accessible versions of PLIP, including a web server, source code, and Jupyter notebooks.
Main Methods:
- PLIP detects eight types of non-covalent interactions.
- The study compared PLIP-identified interactions of the cancer drug venetoclax with the native protein-protein interaction between Bcl-2 and BAX.
- Analysis focused on identifying overlapping interaction profiles between the drug-bound and native protein complexes.
Main Results:
- The enhanced PLIP successfully incorporated protein-protein interaction analysis.
- PLIP analysis showed significant overlap between the interaction profiles of venetoclax and the native Bcl-2/BAX interaction.
- This overlap indicates that venetoclax effectively mimics the native protein-protein interaction.
Conclusions:
- The expanded PLIP tool is valuable for analyzing both small-molecule and protein-protein interactions.
- PLIP can elucidate how drugs modulate biological pathways by mimicking or disrupting native protein interactions.
- The availability of PLIP as a web server and in other formats enhances its accessibility for researchers.
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