Systematic Targeting of Protein-Protein Interactions

Area of Science:

• Drug Discovery
• Structural Biology
• Computational Chemistry

Background:

• Protein-protein interactions (PPIs) were historically considered undruggable targets.
• Recent technological advancements have shifted this perspective, highlighting PPIs as promising therapeutic targets.

Purpose of the Study:

• To review contemporary approaches for discovering inhibitors of protein-protein interactions.
• To focus on a structure-based workflow for inhibitor design.

Main Methods:

• Review of computational analysis, fragment-based screening, and molecular design strategies.
• Detailed examination of a structure-based workflow from target selection to inhibitor design.

Main Results:

• Identification of systematic and complementary workflows for successful PPI inhibitor development.
• Demonstration of strategies to target large protein surfaces with specificity.

Conclusions:

• Protein-protein interactions are increasingly druggable targets.
• Structure-based design workflows are effective for developing specific PPI inhibitors.