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PEDS Advance Access originally published online on June 22, 2007
Protein Engineering Design and Selection 2007 20(6):301-307; doi:10.1093/protein/gzm022
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Proteochemometric modelling of antibody–antigen interactions using SPOT synthesised peptide arrays

Ilona Mandrika, Peteris Prusis, Sviatlana Yahorava, Medya Shikhagaie and Jarl E.S. Wikberg1

Department of Pharmaceutical Biosciences, Pharmacology, Uppsala University, PO Box 591, BMC, SE-751 24 Uppsala, Sweden

1 To whom correspondence should be addressed. E-mail: jarl.wikberg{at}farmbio.uu.se

Proteochemometrics is a technology for the study of molecular recognition based on chemometric techniques. Here we applied it to analyse the amino acids and amino acid physico-chemical properties that are involved in antibodies' recognition of peptide antigens. To this end, we used a study system comprised by a diverse single chain antibody library derived from the murine mAb anti-p24 (HIV-1) antibody CB4-1, evaluated on peptide arrays manufactured by SPOT synthesis. The binding pattern obtained was correlated to physico-chemical descriptors (z-scales) of antibodies and peptides amino acids using partial least-squares projections to latent structures. Cross terms derived from antibody and antigen descriptors were included, which substantially improved the proteochemo-metric model. The final model was statistically highly satisfactory with a correlation coefficient R2 = 0.73 and predictive ability Q2 = 0.68. The physico-chemical properties of each interacting amino acid residue of both the peptides and the antibodies being essential for the antigen–antibody recognition could be retrieved from the model. The study shows for the first time the feasibility of using proteochemometrics to analyse the molecular recognition of antigens by antibodies.

Keywords: antibody interactions/peptide array/proteochemometrics/scFv library/SPOT synthesis

Received November 4, 2006; revised March 31, 2007; accepted April 30, 2007.


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