title: Mass spec studio for integrative structural biology.
abstract: The integration of biophysical data from multiple sources is critical for developing accurate structural models of large multiprotein systems and their regulators. Mass spectrometry (MS) can be used to measure the insertion location for a wide range of topographically sensitive chemical probes, and such insertion data provide a rich, but disparate set of modeling restraints. We have developed a software platform that integrates the analysis of label-based MS and tandem MS (MS(2)) data with protein modeling activities (Mass Spec Studio). Analysis packages can mine any labeling data from any mass spectrometer in a proteomics-grade manner, and link labeling methods with data-directed protein interaction modeling using HADDOCK. Support is provided for hydrogen/deuterium exchange (HX) and covalent labeling chemistries, including novel acquisition strategies such as targeted HX-MS(2) and data-independent HX-MS(2). The latter permits the modeling of highly complex systems, which we demonstrate by the analysis of microtubule interactions.
authors.affiliation: Department of Biochemistry and Molecular Biology and Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Martial
authors.initials: M
authors.lastname: Rey
authors.affiliation: Department of Biochemistry and Molecular Biology and Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sarpe
authors.affiliation: Department of Biochemistry and Molecular Biology and Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Burns
authors.affiliation: Department of Biochemistry and Molecular Biology and Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Joshua
authors.initials: J
authors.lastname: Buse
authors.affiliation: Cultivated Code, Inc., Calgary, AB T2L 2H3, Canada.
authors.forename: Charles A H
authors.initials: CA
authors.lastname: Baker
authors.affiliation: Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Padualaan 8, Utrecht CH 3584, the Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: van Dijk
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195-7290, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Wordeman
authors.affiliation: Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Padualaan 8, Utrecht CH 3584, the Netherlands.
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
authors.affiliation: Department of Biochemistry and Molecular Biology and Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: dschriem@ucalgary.ca.
authors.forename: David C
authors.initials: DC
authors.lastname: Schriemer
mesh_terms: D001665:Binding Sites; D003903:Deuterium; D006859:Hydrogen; D018942:Macrolides / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D040901:Proteomics / Q000379:methods*; D012984:Software; D053719:Tandem Mass Spectrometry / Q000379:methods; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D018942:Macrolides; D014404:Tubulin; C117305:laulimalide; D006859:Hydrogen; D003903:Deuterium