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Antibody Engineering pp 39–55Cite as

Computer-Assisted Modeling of Antibody Variable Domains

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 907))

Abstract

Antibody modeling is an interesting option to gain structure–function insights and to allow rational engineering of these molecules in the absence of experimental data. Among a diversity of algorithms, software packages, and specialized Web servers, the protocol described here presents the following main features: (1) nonautomatic modeling process guided by direct application of antibody modeling principles; (2) local generation of molecular models using free software which can be used in most common operational systems; and (3) the resulting model quality is comparable to models generated by Web servers which represent the current standard of antibody modeling. Briefly, hybrid models of heavy- and light-chain variable domains are separately built by grafting segments from homologous templates (framework regions and complementarity-determining regions). Next, hybrid models are mutated to comply with the target’s sequence and associated by fitting into a template structure that closely matches the predicted packing angle for the target variable domains. After a few cycles of energy minimization the model can be submitted to CDR-H3 optimization or its quality can be directly assessed.

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Abbreviations

VD:

Variable domain

FR:

Framework region

CDR:

Complementarity-determining region

HV:

Antibody heavy-chain variable domain

LV:

Antibody light-chain variable domain

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Author information

Authors and Affiliations

  1. CEA ,iBiTecS, SIMOPRO, Gif-sur-Yvette, France

    Oscar H. P. Ramos

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  1. Oscar H. P. Ramos
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Corresponding author

Correspondence to Oscar H. P. Ramos .

Editor information

Editors and Affiliations

  1. Antibody Therapeutics & Immunotargeting, INSERM U624, Marseille CEDEX 09, France

    Patrick Chames

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© 2012 Springer Science+Business Media, LLC

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Ramos, O.H.P. (2012). Computer-Assisted Modeling of Antibody Variable Domains. In: Chames, P. (eds) Antibody Engineering. Methods in Molecular Biology, vol 907. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-974-7_2

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  • DOI: https://doi.org/10.1007/978-1-61779-974-7_2

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-973-0

  • Online ISBN: 978-1-61779-974-7

  • eBook Packages: Springer Protocols

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