MTMDAT-HADDOCK

MTMDAT-HADDOCK integrates mass spectrometry-derived limited proteolysis data with HADDOCK to map residue-level interaction sites and generate data-driven structural models of protein–protein complexes.

Key Features:

• Integration with HADDOCK: Integrates with the data-driven docking program HADDOCK to create a pipeline for modeling protein–protein complex structures using mass spectrometry data.
• Residue Identification: Identifies residues involved in complex formation by comparing mass spectra from limited proteolysis experiments of bound and unbound proteins.
• Data-Driven Docking: Uses available unbound 3D structures to define restraints that guide data-driven docking in HADDOCK.
• High-Throughput Modeling: Supports high-throughput modeling of multiple protein interactions.
• Validation and Quality Assurance: Validated by comparing models of the Rpn13 ubiquitin-binding domain–ubiquitin interaction to published NMR structures.

Scientific Applications:

• Interaction Site Mapping: Maps amino acid residues involved in protein–protein interfaces based on limited proteolysis mass spectrometry data.
• Protein Stability Analysis: Probes protein stability and identification of stable fragments through limited proteolysis experiments analyzed by mass spectrometry.
• Structural Modeling of Biomolecular Complexes: Generates structural models of protein complexes using MS-derived restraints together with HADDOCK docking.
• Multidomain Protein Studies: Applies to multidomain proteins and biomolecular complexes to localize interaction sites at residue resolution.

Methodology:

Analyzes mass spectrometry data from limited proteolysis experiments to identify stable fragments and residues affected by binding by comparing bound and unbound spectra, then uses identified sites and available unbound 3D structures to define restraints for data-driven docking in HADDOCK.