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

Protein Eng Des Sel. 2007 Jun;20(6):301-7. doi: 10.1093/protein/gzm022. Epub 2007 Jun 22.

Abstract

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 proteochemometric model. The final model was statistically highly satisfactory with a correlation coefficient R(2) = 0.73 and predictive ability Q(2) = 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / genetics
  • Antigen-Antibody Reactions*
  • Combinatorial Chemistry Techniques
  • Feasibility Studies
  • HIV Core Protein p24 / immunology*
  • Immunoglobulin Variable Region / chemistry*
  • Immunoglobulin Variable Region / genetics
  • Mice
  • Models, Chemical
  • Mutation
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Protein Array Analysis / methods

Substances

  • Amino Acids
  • Antibodies, Monoclonal
  • HIV Core Protein p24
  • Immunoglobulin Variable Region
  • Peptides