Skip to main content
SpringerLink
Log in

Protein Sequence and Structure Analysis of Antibody Variable Domains

  • Protocol
Antibody Engineering

Part of the book series: Springer Protocols Handbooks ((SPH))

Abstract

The protocols described here provide methods for computational analysis of antibody sequence and structure. With the availability of the World Wide Web, many online analysis tools have been made available, and URLs for these are cited throughout the text. The author has provided a Web site at http://www.bioinf.org.uk/abs/labmanual/ containing links to all the tools described here.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abhinandan KR, Martin ACR (2008) Analysis and improvements to Kabat and structurally correct numbering of antibody variable domains. Mol Immunol 45:3832–3839

    Article  PubMed  CAS  Google Scholar 

  • Abhinandan KR, Martin ACR (in preparation) Analysis and prediction of VH/VL packing in antibodies

    Google Scholar 

  • Al-Lazikani B, Lesk AM, Chothia C (1997) Standard conformations for the canonical structures of immunoglobulins. J Mol Biol 273:927–948

    Article  PubMed  CAS  Google Scholar 

  • Allcorn LC, Martin ACR (2002) SACS-self-maintaining database of antibody crystal structure information. Bioinformatics 18:175–181

    Article  PubMed  CAS  Google Scholar 

  • Alzari PM, Lascombe M-B, Poljak RJ (1988) Three-dimensional structure of antibodies. Annu Rev Immunol 6:555–580

    Article  PubMed  CAS  Google Scholar 

  • Amit AG, Mariuzza RA, Phillips SEV, Poljak RJ (1985) Three-dimensional structure of an antigen–antibody complex at 6 Ã… resolution. Nature (London) 313:156–158

    Article  CAS  Google Scholar 

  • Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucl Acids Res 28:235–242

    Article  PubMed  CAS  Google Scholar 

  • Brochet X, Lefranc M-P, Giudicelli V (2008) IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucl Acids Res 36:W503–W508

    Article  PubMed  CAS  Google Scholar 

  • Bruccoleri RE, Karplus M (1987) Prediction of the folding of short polypeptide segments by uniform conformational sampling. Biopolymers 26:137–168

    Article  PubMed  CAS  Google Scholar 

  • Chothia C, Janin J (1981) Relative orientation of close-packed β-pleated sheets in proteins. Proc Natl Acad Sci USA 78:4146–4150

    Article  PubMed  CAS  Google Scholar 

  • Chothia C, Lesk AM, Tramontano A, Levitt M, Smith-Gill SJ, Air G, Sheriff S, Padlan EA, Davies D, Tulip WR, Colman PM, Spinelli S, Alzari PM, Poljak RJ (1989) Conformations of immunoglobulin hypervariable regions. Nature (London) 342:877–883

    Article  CAS  Google Scholar 

  • Davies DR, Padlan EA, Sheriff S (1990) Antibody–antigen complexes. Annu Rev Biochem 59:439–473

    Article  PubMed  CAS  Google Scholar 

  • Deret S, Maissiat C, Aucouturier P, Chomilier J (1995) SUBIM: A program for analysing the Kabat database and determining the variability subgroup of a new immunoglobulin sequence. Comput Appl Biosci 11:435–439

    PubMed  CAS  Google Scholar 

  • Edelman GM (1970) The covalent structure of a human γ-immunoglobulin: XI functional implications. Biochemistry 9:3197–3205

    Article  PubMed  CAS  Google Scholar 

  • Edelman GM, Gall WE (1969) The antibody problem. Annu Rev Biochem 38:415–466

    Article  PubMed  CAS  Google Scholar 

  • Giudicelli V, Chaume D, Bodmer J, Müller W, Busin C, Marsh S, Bontrop R, Marc L, Malik A, Lefranc MP (1997) IMGT, the international ImMunoGeneTics database. Nucl Acids Res 25:206–211

    Article  PubMed  CAS  Google Scholar 

  • Giudicelli V, Duroux P, Ginestoux C, Folch G, Jabado-Michaloud J, Chaume D, Lefranc M-P (2006) IMGT/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences. Nucl Acids Res 34:D781–D784

    Article  PubMed  CAS  Google Scholar 

  • Honegger A, Plückthun A (2001) Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool. J Mol Biol 309:657–670

    Article  PubMed  CAS  Google Scholar 

  • Huber R, Bennett WS (1987) Antibody–antigen flexibility. Nature (London) 326:334–335

    Article  CAS  Google Scholar 

  • Kabat EA, Wu TT, Perry HM, Gottesman KS, Foeller C (1991) Sequences of proteins of immunological interest, 5th edn. U.S. Department of Health and Human Services, National Institutes for Health, Bethesda, MD

    Google Scholar 

  • Lefranc M-P, Pommié C, Ruiz M, Giudicelli V, Foulquier E, Truong L, Thouvenin-Contet V, Lefranc G (2003) IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev Comp Immunol 27:55–77

    Article  PubMed  CAS  Google Scholar 

  • Lesk AM, Chothia C (1982) Evolution of proteins formed by β-sheets: II. The core of the immunoglobulin domains. J Mol Biol 160:325–342

    Article  PubMed  CAS  Google Scholar 

  • MacCallum RM, Martin AC, Thornton JM (1996) Antibody–antigen interactions: Contact analysis and binding site topography. J Mol Biol 262:732–745

    Article  PubMed  CAS  Google Scholar 

  • Mariuzza RA, Phillips SEV, Poljak RJ (1987) The structural basis of antigen–antibody recognition. Annu Rev Biophys Bioeng 16:139–159

    Article  CAS  Google Scholar 

  • Martin ACR (1996) Accessing the Kabat antibody sequence database by computer. Proteins Struct Funct Genet 25:130–133

    Article  PubMed  CAS  Google Scholar 

  • Martin ACR, Thornton JM (1996) Structural families in homologous proteins: Automatic classification, modelling and application to antibodies. J Mol Biol 263:800–815

    Article  PubMed  CAS  Google Scholar 

  • Martin ACR, Cheetham JC, Rees AR (1989) Modelling antibody hypervariable loops: A combined algorithm. Proc Natl Acad Sci USA 86:9268–9272

    Article  PubMed  CAS  Google Scholar 

  • Padlan EA (1977) The structural basis for the specificity of antibody–antigen reactions and structural mechanisms for the diversification of antigen-binding specificities. Quant Rev Biophys 10:35–65

    Article  CAS  Google Scholar 

  • Padlan EA (1994) Anatomy of the antibody molecule. Mol Immunol 31:169–217

    Article  PubMed  CAS  Google Scholar 

  • Poljak RJ, Amzel LM, Avey HP, Chen BL, Phizackerley RP, Saul F (1973) The three-dimensional structure of the Fab′ fragment of a human immunoglobulin at 2.8 Ã… resolution. Proc Natl Acad Sci USA 70:3305–3310

    Article  PubMed  CAS  Google Scholar 

  • Porter RR (1959) The hydrolysis of rabbit γ-globulin and antibodies with crystalline papain. Biochem J 73:119–127

    PubMed  CAS  Google Scholar 

  • Saldanha JW, Martin AC, Léger OJ (1999) A single backmutation in the human κIV framework of a previously unsuccessfully humanized antibody restores the binding activity and increases the secretion in cos cells. Mol Immunol 36:709–719

    Article  PubMed  CAS  Google Scholar 

  • Searle SJ, Pedersen JT, Henry AH, Webster DM, Rees AR (1994) Antibody structure and function. In: Borreback CAK (ed) Antibody engineering. Oxford University Press, London, pp 3–51

    Google Scholar 

  • Sivasubramanian A, Sircar A, Chaudhury A, Gray JJ (2009) Toward high-resolution homology modeling of antibody Fv regions and application to antibody–antigen docking. Proteins 74:497–514

    Article  PubMed  CAS  Google Scholar 

  • Valentine RC, Green NM (1967) Electron microscopy of an antibody–hapten complex. J Mol Biol 27:615–617

    Article  PubMed  CAS  Google Scholar 

  • Wilson IA, Stanfield RL (1993) Antibody–antigen interactions. Curr Opin Struct Biol 3:113–118

    Article  CAS  Google Scholar 

  • Wu TT, Kabat EA (1970) An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med 132:211–250

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Structural and Molecular Biology, Darwin Building, University College London, Gower Street, London, WC1E 6BT, UK

    Andrew C. R. Martin

Authors
  1. Andrew C. R. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew C. R. Martin .

Editor information

Editors and Affiliations

  1. (Biomedical Engineering) Institut für Zellbiologie und Immunologie, Universität Stuttgart, Allmandring 31, 70569, Stuttgart, Germany

    Roland Kontermann

  2. Technische Universität Braunschweig, Institut für Biochemie und Biotechnologie, Spielmannstraße 7, 38106, Braunschweig, Germany

    Stefan Dübel

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this protocol

Cite this protocol

Martin, A.C.R. (2010). Protein Sequence and Structure Analysis of Antibody Variable Domains. In: Kontermann, R., Dübel, S. (eds) Antibody Engineering. Springer Protocols Handbooks. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-01147-4_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-01147-4_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-01146-7

  • Online ISBN: 978-3-642-01147-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation