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 computational models of the assembly structures that are consistent with all of the available datasets. 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 much 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, California Institute for Quantitative Biosciences, University of California, San Francisco, CA, USA. ben@salilab.org
authors.forename: Benjamin
authors.initials: B
authors.lastname: Webb
authors.forename: Keren
authors.initials: K
authors.lastname: Lasker
authors.forename: Dina
authors.initials: D
authors.lastname: Schneidman-Duhovny
authors.forename: Elina
authors.initials: E
authors.lastname: Tjioe
authors.forename: Jeremy
authors.initials: J
authors.lastname: Phillips
authors.forename: Seung Joong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Javier
authors.initials: J
authors.lastname: Velázquez-Muriel
authors.forename: Daniel
authors.initials: D
authors.lastname: Russel
authors.forename: Andrej
authors.initials: A
authors.lastname: Sali
mesh_terms: D019295:Computational Biology / Q000379:methods*; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012984:Software
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins