title: Proteochemometric modelling of antibody-antigen interactions using SPOT synthesised peptide arrays.
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.
authors.affiliation: Department of Pharmaceutical Biosciences, Pharmacology, Uppsala University, PO Box 591, BMC, SE-751 24 Uppsala, Sweden.
authors.forename: Ilona
authors.initials: I
authors.lastname: Mandrika
authors.forename: Peteris
authors.initials: P
authors.lastname: Prusis
authors.forename: Sviatlana
authors.initials: S
authors.lastname: Yahorava
authors.forename: Medya
authors.initials: M
authors.lastname: Shikhagaie
authors.forename: Jarl E S
authors.initials: JE
authors.lastname: Wikberg
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics; D000937:Antigen-Antibody Reactions; D020650:Combinatorial Chemistry Techniques; D005240:Feasibility Studies; D016655:HIV Core Protein p24 / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008956:Models, Chemical; D009154:Mutation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D040081:Protein Array Analysis / Q000379:methods
chemical_list: D000596:Amino Acids; D000911:Antibodies, Monoclonal; D016655:HIV Core Protein p24; D007135:Immunoglobulin Variable Region; D010455:Peptides