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

Fingerprint

Antibodies
Complementarity Determining Regions
Conformations
Antigens
Network protocols
Program processors
Supercomputers
Grafts
Uncertainty
Servers
Transplants
Computer simulation
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Weitzner, B. D., Jeliazkov, J. R., Lyskov, S., Marze, N., Kuroda, D., Frick, R., ... 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

Modeling and docking of antibody structures with Rosetta. / Weitzner, Brian D.; Jeliazkov, Jeliazko R.; Lyskov, Sergey; Marze, Nicholas; Kuroda, Daisuke; Frick, Rahel; Adolf-Bryfogle, Jared; Biswas, Naireeta; Dunbrack, Roland L.; Gray, Jeffrey J.

In: Nature Protocols, Vol. 12, No. 2, 01.02.2017, p. 401-416.

Research output: Contribution to journalArticle

Weitzner, BD, Jeliazkov, JR, Lyskov, S, Marze, N, Kuroda, D, Frick, R, Adolf-Bryfogle, J, Biswas, N, Dunbrack, RL & Gray, JJ 2017, 'Modeling and docking of antibody structures with Rosetta', Nature Protocols, vol. 12, no. 2, pp. 401-416. https://doi.org/10.1038/nprot.2016.180
Weitzner BD, Jeliazkov JR, Lyskov S, Marze N, Kuroda D, Frick R et al. Modeling and docking of antibody structures with Rosetta. Nature Protocols. 2017 Feb 1;12(2):401-416. https://doi.org/10.1038/nprot.2016.180
Weitzner, Brian D. ; Jeliazkov, Jeliazko R. ; Lyskov, Sergey ; Marze, Nicholas ; Kuroda, Daisuke ; Frick, Rahel ; Adolf-Bryfogle, Jared ; Biswas, Naireeta ; Dunbrack, Roland L. ; Gray, Jeffrey J. / Modeling and docking of antibody structures with Rosetta. In: Nature Protocols. 2017 ; Vol. 12, No. 2. pp. 401-416.
@article{713c612415514f3caf5e8d7fd06051df,
title = "Modeling and docking of antibody structures with Rosetta",
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.",
author = "Weitzner, {Brian D.} and Jeliazkov, {Jeliazko R.} and Sergey Lyskov and Nicholas Marze and Daisuke Kuroda and Rahel Frick and Jared Adolf-Bryfogle and Naireeta Biswas and Dunbrack, {Roland L.} and Gray, {Jeffrey J}",
year = "2017",
month = "2",
day = "1",
doi = "10.1038/nprot.2016.180",
language = "English (US)",
volume = "12",
pages = "401--416",
journal = "Nature Protocols",
issn = "1754-2189",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Modeling and docking of antibody structures with Rosetta

AU - Weitzner, Brian D.

AU - Jeliazkov, Jeliazko R.

AU - Lyskov, Sergey

AU - Marze, Nicholas

AU - Kuroda, Daisuke

AU - Frick, Rahel

AU - Adolf-Bryfogle, Jared

AU - Biswas, Naireeta

AU - Dunbrack, Roland L.

AU - Gray, Jeffrey J

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85010932843&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010932843&partnerID=8YFLogxK

U2 - 10.1038/nprot.2016.180

DO - 10.1038/nprot.2016.180

M3 - Article

C2 - 28125104

AN - SCOPUS:85010932843

VL - 12

SP - 401

EP - 416

JO - Nature Protocols

JF - Nature Protocols

SN - 1754-2189

IS - 2

ER -