PdCSM-PPI: Using Graph-Based Signatures to Identify Protein-Protein Interaction Inhibitors

Abstract

Protein-protein interactions are promising sites for development of selective drugs; however, they have generally been viewed as challenging targets. Molecules targeting protein-protein interactions tend to be larger and more lipophilic than other drug-like molecules, mimicking the properties of interacting interfaces. Here, we propose a machine learning approach that uses a graph-based representation of small molecules to guide identification of inhibitors modulating protein-protein interactions, pdCSM-PPI. This approach was applied to 21 different PPI targets. We developed interaction-specific models that were able to accurately identify active compounds achieving MCC and F1 scores up to 1..