Mandrika Ilona, Prusis Peteris, Yahorava Sviatlana, Shikhagaie Medya, Wikberg Jarl E S
Department of Pharmaceutical Biosciences, Pharmacology, Uppsala University, PO Box 591, BMC, SE-751 24 Uppsala, Sweden.
Protein Eng Des Sel. 2007 Jun;20(6):301-7. doi: 10.1093/protein/gzm022. Epub 2007 Jun 22.
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.
蛋白质化学计量学是一种基于化学计量学技术研究分子识别的技术。在此，我们将其应用于分析参与抗体对肽抗原识别的氨基酸及其物理化学性质。为此，我们使用了一个研究系统，该系统由源自鼠抗 p24（HIV-1）抗体 CB4-1 的多样化单链抗体库组成，并在通过 SPOT 合成制造的肽阵列上进行评估。使用偏最小二乘投影到潜在结构的方法，将获得的结合模式与抗体和肽氨基酸的物理化学描述符（z 标度）相关联。纳入了源自抗体和抗原描述符的交叉项，这显著改进了蛋白质化学计量学模型。最终模型在统计学上非常令人满意，相关系数 R(2) = 0.73，预测能力 Q(2) = 0.68。从该模型中可以检索到肽和抗体中每个相互作用氨基酸残基的物理化学性质，这些性质对于抗原-抗体识别至关重要。该研究首次展示了使用蛋白质化学计量学分析抗体对抗原分子识别的可行性。
