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MTMDAT-HADDOCK: high-throughput, protein complex structure modeling based on limited proteolysis and mass
Janosch Hennig1, Sjoerd J de Vries, Klaus Dm Hennig
1Department of Physics, Chemistry, and Biology, Linköping University, SE-581 83 Linköping, Sweden. janosch.hennig@helmholtz-muenchen.de
BMC Structural Biology
|November 17, 2012
Summary
A new pipeline integrates MTMDAT and HADDOCK for high-throughput protein complex modeling using mass spectrometry data. This method accurately predicts complex structures, aiding in understanding protein interactions and stability.
Area of Science:
- Structural Biology
- Biochemistry
- Computational Biology
Background:
- Limited proteolysis coupled with mass spectrometry (MTMDAT) analyzes protein structure and interactions.
- This technique reveals stable protein fragments, tertiary/quaternary structure, and residue-level stability changes.
- Protein-protein complex analysis is crucial for understanding cellular functions.
Purpose of the Study:
- Introduce a streamlined pipeline integrating MTMDAT and HADDOCK for automated protein complex structure determination.
- Enable high-throughput modeling of protein complexes using mass spectrometry data.
- Validate the pipeline's accuracy by comparing modeled structures with experimental data.
Main Methods:
- Utilized MTMDAT for analyzing limited proteolysis mass spectrometry data to identify protein-protein interaction interfaces.
- Developed a pipeline connecting MTMDAT with HADDOCK for data-driven protein complex modeling.
- Employed ubiquitin and the ubiquitin-binding domain of Rpn13 as a model system for validation.
Main Results:
- MTMDAT can directly identify residues involved in complex formation by comparing bound and unbound protein mass spectra.
- The integrated MTMDAT-HADDOCK pipeline enables high-throughput modeling of protein complexes.
- The resulting structural model showed comparable quality to NMR-derived structures.
Conclusions:
- The MTMDAT-HADDOCK pipeline facilitates direct, high-throughput modeling of protein complexes from mass spectrometry data.
- The software is available for academic/non-commercial use.
- This approach enhances the study of protein-protein interactions and complex stability.
