Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019:2022:353-377.
doi: 10.1007/978-1-4939-9608-7_15.

Modeling Biological Complexes Using Integrative Modeling Platform

Daniel Saltzberg  1 , Charles H Greenberg  1 , Shruthi Viswanath  1 , Ilan Chemmama  1 , Ben Webb  1 , Riccardo Pellarin  2 , Ignacia Echeverria  1 , Andrej Sali  3
Affiliations

Modeling Biological Complexes Using Integrative Modeling Platform

Daniel Saltzberg et al. Methods Mol Biol. 2019.

Abstract

Integrative structure modeling provides 3D models of macromolecular systems that are based on information from multiple types of experiments, physical principles, statistical inferences, and prior structural models. Here, we provide a hands-on realistic example of integrative structure modeling of the quaternary structure of the actin, tropomyosin, and gelsolin protein assembly based on electron microscopy, solution X-ray scattering, and chemical crosslinking data for the complex as well as excluded volume, sequence connectivity, and rigid atomic X-ray structures of the individual subunits. We follow the general four-stage process for integrative modeling, including gathering the input information, converting the input information into a representation of the system and a scoring function, sampling alternative model configurations guided by the scoring function, and analyzing the results. The computational aspects of this approach are implemented in our open-source Integrative Modeling Platform (IMP), a comprehensive and extensible software package for integrative modeling ( https://integrativemodeling.org ). In particular, we rely on the Python Modeling Interface (PMI) module of IMP that provides facile mixing and matching of macromolecular representations, restraints based on different types of information, sampling algorithms, and analysis including validations of the input data and output models. Finally, we also outline how to deposit an integrative structure and corresponding experimental data into PDB-Dev, the nascent worldwide Protein Data Bank (wwPDB) resource for archiving and disseminating integrative structures ( https://pdb-dev.wwpdb.org ). The example application provides a starting point for a user interested in using IMP for integrative modeling of other biomolecular systems.

Keywords: Biomolecular simulation; Biophysical data; Integrative modeling; Structural modeling.

PubMed Disclaimer

Similar articles

  • IHMCIF: An Extension of the PDBx/mmCIF Data Standard for Integrative Structure Determination Methods.
    Vallat B, Webb BM, Westbrook JD, Goddard TD, Hanke CA, Graziadei A, Peisach E, Zalevsky A, Sagendorf J, Tangmunarunkit H, Voinea S, Sekharan M, Yu J, Bonvin AAMJJ, DiMaio F, Hummer G, Meiler J, Tajkhorshid E, Ferrin TE, Lawson CL, Leitner A, Rappsilber J, Seidel CAM, Jeffries CM, Burley SK, Hoch JC, Kurisu G, Morris K, Patwardhan A, Velankar S, Schwede T, Trewhella J, Kesselman C, Berman HM, Sali A. Vallat B, et al. J Mol Biol. 2024 Sep 1;436(17):168546. doi: 10.1016/j.jmb.2024.168546. Epub 2024 Mar 18. J Mol Biol. 2024. PMID: 38508301 Free PMC article.
  • Archiving and disseminating integrative structure models.
    Vallat B, Webb B, Westbrook J, Sali A, Berman HM. Vallat B, et al. J Biomol NMR. 2019 Jul;73(6-7):385-398. doi: 10.1007/s10858-019-00264-2. Epub 2019 Jul 5. J Biomol NMR. 2019. PMID: 31278630 Free PMC article.
  • Protein Data Bank (PDB): The Single Global Macromolecular Structure Archive.
    Burley SK, Berman HM, Kleywegt GJ, Markley JL, Nakamura H, Velankar S. Burley SK, et al. Methods Mol Biol. 2017;1607:627-641. doi: 10.1007/978-1-4939-7000-1_26. Methods Mol Biol. 2017. PMID: 28573592 Free PMC article. Review.
  • The Protein Data Bank Archive.
    Velankar S, Burley SK, Kurisu G, Hoch JC, Markley JL. Velankar S, et al. Methods Mol Biol. 2021;2305:3-21. doi: 10.1007/978-1-0716-1406-8_1. Methods Mol Biol. 2021. PMID: 33950382 Review.
  • PDBx/mmCIF Ecosystem: Foundational Semantic Tools for Structural Biology.
    Westbrook JD, Young JY, Shao C, Feng Z, Guranovic V, Lawson CL, Vallat B, Adams PD, Berrisford JM, Bricogne G, Diederichs K, Joosten RP, Keller P, Moriarty NW, Sobolev OV, Velankar S, Vonrhein C, Waterman DG, Kurisu G, Berman HM, Burley SK, Peisach E. Westbrook JD, et al. J Mol Biol. 2022 Jun 15;434(11):167599. doi: 10.1016/j.jmb.2022.167599. Epub 2022 Apr 20. J Mol Biol. 2022. PMID: 35460671 Free PMC article. Review.
See all similar articles

Cited by

See all "Cited by" articles

Substances

LinkOut - more resources