title: Modeling of proteins and their assemblies with the Integrative Modeling Platform.
abstract: To understand the workings of the living cell, we need to characterize protein assemblies that constitute the cell (for example, the ribosome, 26S proteasome, and the nuclear pore complex). A reliable high-resolution structural characterization of these assemblies is frequently beyond the reach of current experimental methods, such as X-ray crystallography, NMR spectroscopy, electron microscopy, footprinting, chemical cross-linking, FRET spectroscopy, small angle X-ray scattering, and proteomics. However, the information garnered from different methods can be combined and used to build models of the assembly structures that are consistent with all of the available datasets, and therefore more accurate, precise, and complete. Here, we describe a protocol for this integration, whereby the information is converted to a set of spatial restraints and a variety of optimization procedures can be used to generate models that satisfy the restraints as well as possible. These generated models can then potentially inform about the precision and accuracy of structure determination, the accuracy of the input datasets, and further data generation. We also demonstrate the Integrative Modeling Platform (IMP) software, which provides the necessary computational framework to implement this protocol, and several applications for specific use cases.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quanstitative Biosciences (QB3), University of California San Francisco, San Francisco, CA, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Webb
authors.forename: Keren
authors.initials: K
authors.lastname: Lasker
authors.forename: Javier
authors.initials: J
authors.lastname: Velázquez-Muriel
authors.forename: Dina
authors.initials: D
authors.lastname: Schneidman-Duhovny
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pellarin
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bonomi
authors.forename: Charles
authors.initials: C
authors.lastname: Greenberg
authors.forename: Barak
authors.initials: B
authors.lastname: Raveh
authors.forename: Elina
authors.initials: E
authors.lastname: Tjioe
authors.forename: Daniel
authors.initials: D
authors.lastname: Russel
authors.forename: Andrej
authors.initials: A
authors.lastname: Sali
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods; D008854:Microscopy, Electron; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011381:Programming Languages; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics; D053838:Scattering, Small Angle; D064878:Web Browser; D014961:X-Ray Diffraction
chemical_list: D011506:Proteins