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Nat Protoc. 2017 Feb;12(2):401-416. doi: 10.1038/nprot.2016.180. Epub 2017 Jan 26.

Modeling and docking of antibody structures with Rosetta.

Author information

1
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
2
Program in Molecular Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.
3
Department of Analytical and Physical Chemistry, Showa University School of Pharmacy, Tokyo, Japan.
4
Centre for Immune Regulation, Department of Biosciences, University of Oslo, Oslo, Norway.
5
Centre for Immune Regulation, Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
6
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
7
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
8
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland, USA.
9
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

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.

PMID:
28125104
PMCID:
PMC5739521
DOI:
10.1038/nprot.2016.180
[Indexed for MEDLINE]
Free PMC Article

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