W524 Nucleic Acids Research, 2012, Vol. 40, Web Server issue research and for applications aimed at modifying and manipulating such interactions. Paratome provides a simple interface for the identiﬁcation of the Ag-binding regions from the amino acid sequence or 3D structure of an Ab and has been shown to do so efﬁciently. Considering that the 3D structure of most known Abs is yet unknown, the ability to accurately and reliably identify the ABRs directly from sequence, is highly valuable and increases the accessibility of this essential knowledge to the entire scientiﬁc community in general and to immunity researchers in particular. SUPPLEMENTARY DATA Supplementary Data are available at Supplementary Data 1–3. NAR Online: ACKNOWLEDGEMENTS Thanks to Inbal Sela, Anat Burkovitz and Guy Nimrod for their help in testing and feedback on the server and manuscript. FUNDING Funding for open access charge: Research grant from the Israel Science Foundation [511]. Conﬂict of interest statement. None declared. REFERENCES 1. Chan,A.C. and Carter,P.J. (2010) Therapeutic antibodies for autoimmunity and inﬂammation. Nat. Rev., 10, 301–316. 2. Verhoeyen,M., Milstein,C. and Winter,G. (1988) Reshaping human antibodies: grafting an antilysozyme activity. Science, 239, 1534–1536. 3. Almagro,J.C. (2004) Identiﬁcation of differences in the speciﬁcity-determining residues of antibodies that recognize antigens of different size: implications for the rational design of antibody repertoires. J. Mol. Recognit., 17, 132–143. 4. Lou,J. and Marks,J.D. (2010) Afﬁnity maturation by chain shufﬂing and site directed mutagenesis. In: Kontermann,F. and Du¨ bel,S. (eds), In: Antibody Engineering, Part IV. Springer Berlin Heidelberg, pp. 377–396. 5. Schrama,D., Reisfeld,R.A. and Becker,J.C. (2006) Antibody targeted drugs as cancer therapeutics. Nat. Rev. Drug Discov., 5, 147–159. 6. Hawkins,R.E., Russell,S.J. and Winter,G. (1992) Selection of phage antibodies by binding afﬁnity. Mimicking afﬁnity maturation. J. Mol. Biol., 226, 889–896. 7. Jones,P.T., Dear,P.H., Foote,J., Neuberger,M.S. and Winter,G. (1986) Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature, 321, 522–525. 8. MacCallum,R.M., Martin,A.C. and Thornton,J.M. (1996) Antibody-antigen interactions: contact analysis and binding site topography. J. Mol. Biol., 262, 732–745. 9. Padlan,E.A., Abergel,C. and Tipper,J.P. (1995) Identiﬁcation of speciﬁcity-determining residues in antibodies. FASEB J., 9, 133–139. 10. Wu,T.T. and Kabat,E.A. (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. 11. Al-Lazikani,B., Lesk,A.M. and Chothia,C. (1997) Standard conformations for the canonical structures of immunoglobulins. J. Mol. Biol., 273, 927–948. 12. Chothia,C. and Lesk,A.M. (1987) Canonical structures for the hypervariable regions of immunoglobulins. J. Mol. Biol., 196, 901–917. 13. Chothia,C., Lesk,A.M., Tramontano,A., Levitt,M., Smith- Gill,J.S., Air,G., Sheriff,S., Padlan,E.A., Davies,D., Tulip,W.R. et al. (1989) Conformations of immunoglobulin hypervariable regions. Nature, 342, 877–883. 14. Kabat,E.A., Wu,T.T. and Bilofsky,H. (1977) Unusual distributions of amino acids in complementarity-determining (hypervariable) segments of heavy and light chains of immunoglobulins and their possible roles in speciﬁcity of antibody-combining sites. J. Biol. Chem., 252, 6609–6616. 15. Kabat,E.A., Wu,T.T., Bilofsky,H., Reid-Miller,M. and Perry,H. (1983) Sequence of Proteins of Immunological Interest. National Institute of Health, Bathesda. 16. Lefranc,M.P., Pommie,C., Ruiz,M., Giudicelli,V., Foulquier,E., Truong,L., Thouvenin-Contet,V. and 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. 17. Padlan,E.A. (1977) Structural implications of sequence variability in immunoglobulins. Proc. Natl Acad. Sci. USA, 74, 2551–2555. 18. Kunik,V., Peters,B. and Ofran,Y. (2012) Structural Consensus among Antibodies Deﬁnes the Antigen Binding Site. PLoS Comput. Biol., 8, e1002388. 19. Ofran,Y., Schlessinger,A. and Rost,B. (2008) Automated identiﬁcation of complementarity determining regions (CDRs) reveals peculiar characteristics of CDRs and B cell epitopes. J. Immunol., 181, 6230–6235. 20. Altschul,S.F., Madden,T.L., Schaffer,A.A., Zhang,J., Zhang,Z., Miller,W. and Lipman,D.J. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res., 25, 3389–3402. 21. Smith,T.F. and Waterman,M.S. (1981) Identiﬁcation of common molecular subsequences. J. Mol. Biol., 147, 195–197. 22. Shindyalov,I.N. and Bourne,P.E. (1998) Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. Protein Eng., 11, 739–747. 23. Ofran,Y. and Rost,B. (2003) Analysing six types of protein-protein interfaces. J. Mol. Biol., 325, 377–387.