%0 Journal Article
%T MTMDAT-HADDOCK: High-throughput, protein complex structure modeling based on limited proteolysis and mass spectrometry
%A Janosch Hennig
%A Sjoerd J de Vries
%A Klaus DM Hennig
%A Leah Randles
%A Kylie J Walters
%A Maria Sunnerhagen
%A Alexandre MJJ Bonvin
%J BMC Structural Biology
%D 2012
%I BioMed Central
%R 10.1186/1472-6807-12-29
%X A new feature of MTMDAT allows for the direct identification of residues that are involved in complex formation by comparing the mass spectra of bound and unbound proteins after proteolysis. If 3D structures of the unbound components are available, this data can be used to define restraints for data-driven docking to calculate a model of the complex. We describe here a new implementation of MTMDAT, which includes a pipeline to the data-driven docking program HADDOCK, thus streamlining the entire procedure. This addition, together with usability improvements in MTMDAT, enables high-throughput modeling of protein complexes from mass spectrometry data. The algorithm has been validated by using the protein-protein interaction between the ubiquitin-binding domain of proteasome component Rpn13 and ubiquitin. The resulting structural model, based on restraints extracted by MTMDAT from limited proteolysis and modeled by HADDOCK, was compared to the published NMR structure, which relied on twelve unambiguous intermolecular NOE interactions. The MTMDAT-HADDOCK structure was of similar quality to structures generated using only chemical shift perturbation data derived by NMR titration experiments.The new MTMDAT-HADDOCK pipeline enables direct high-throughput modeling of protein complexes from mass spectrometry data. MTMDAT-HADDOCK can be downloaded from http://www.ifm.liu.se/chemistry/molbiotech/maria_sunnerhagens_group/mtmdat/ webcitetogether with the manual and example files. The program is free for academic/non-commercial purposes.It remains a major undertaking in the post-genome era to determine which biomolecules interact with each other, what function they have and to obtain their three dimensional high resolution structures. The main methods for achieving the latter are crystallography and nuclear magnetic resonance (NMR) spectroscopy, both of which can be time-consuming despite significant methodological advances. In addition, many targets elude high-resolution structu
%U http://www.biomedcentral.com/1472-6807/12/29