MGTbind: a comprehensive database of molecular glue ternary interactome

Area of Science:

• Biochemistry
• Chemical Biology
• Drug Discovery

Background:

• Molecular glues (MGs) are small molecules that modulate protein-protein interactions, impacting cellular functions.
• MG discovery is currently limited by serendipity and extensive experimental screening.
• There is a growing need for data-driven approaches to facilitate rational MG design.

Purpose of the Study:

• To develop a comprehensive database (MGTbind) for molecular glue and ternary binding information.
• To provide curated data resources supporting the rational design of molecular glues.
• To facilitate research in drug discovery and synthetic biology by offering insights into the MG-engaged interactome.

Main Methods:

• Manual curation of 3093 molecular glues, including chemical structures and properties.
• Integration of 3924 ternary interactions with associated bioactivity measurements (degradation, in vitro, cellular).
• Systematic collection of ternary complex structural data from PDB and AlphaFold 3 predictions.

Main Results:

• The MGTbind database contains extensive data on MGs, their chemical properties, and interactions.
• Bioactivity measurements and hierarchical binding affinities are included to analyze cooperative binding.
• Structural data from PDB and AlphaFold 3 are integrated for intuitive analysis and visualization.

Conclusions:

• The MGTbind database provides a valuable resource for advancing molecular glue research.
• It enables intuitive analysis and visualization of MG-engaged ternary complexes.
• The freely accessible web interface supports global search and browsing for researchers in drug discovery and synthetic biology.