Modeling and docking of antibody structures with Rosetta

Brian D. Weitzner, Jeliazko R. Jeliazkov, Sergey Lyskov, Nicholas Marze, Daisuke Kuroda, Rahel Frick, Jared Adolf-Bryfogle, Naireeta Biswas, Roland L. Dunbrack, Jeffrey J. Gray

Research output: Contribution to journalArticle

Abstract

We describe Rosetta-based computational protocols for predicting the 3D structure of an antibody from sequence (RosettaAntibody) and then docking the antibody to protein antigens (SnugDock). Antibody modeling leverages canonical loop conformations to graft large segments from experimentally determined structures, as well as offering (i) energetic calculations to minimize loops, (ii) docking methodology to refine the VL-VH relative orientation and (iii) de novo prediction of the elusive complementarity determining region (CDR) H3 loop. To alleviate model uncertainty, antibody-antigen docking resamples CDR loop conformations and can use multiple models to represent an ensemble of conformations for the antibody, the antigen or both. These protocols can be run fully automated via the ROSIE web server (http://rosie.rosettacommons.org/) or manually on a computer with user control of individual steps. For best results, the protocol requires roughly 1,000 CPU-hours for antibody modeling and 250 CPU-hours for antibody-antigen docking. Tasks can be completed in under a day by using public supercomputers.

Original languageEnglish (US)
Pages (from-to)401-416
Number of pages16
JournalNature protocols
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Weitzner, B. D., Jeliazkov, J. R., Lyskov, S., Marze, N., Kuroda, D., Frick, R., Adolf-Bryfogle, J., Biswas, N., Dunbrack, R. L., & Gray, J. J. (2017). Modeling and docking of antibody structures with Rosetta. Nature protocols, 12(2), 401-416. https://doi.org/10.1038/nprot.2016.180