Computer-Aided Molecular Modeling Study on Antibody Recognition of Small Molecules: An Immunoassay for Triazine Herbicides

Abstract

Most immunoassays for determination of small molecules are still designed on the basis of the "trial and error" method, due to the lack of understanding of antibody recognition. In the present study, we developed a heterologous indirect competitive enzyme-linked immunosorbent assay for determination of triazine herbicides, with limits of detection for 11 triazines ranging from 0.05 to 29.4 μg/L. Mechanisms of the antigen-antibody interaction were studied by computer-aided molecular modeling (CAMM)-based quantitative structure-activity relationship analyses. Co-effects of the analytes' substructural hydrophobic, electrostatic, and steric fields on antibody recognition were further revealed. Hydrophobicity of the antigens was demonstrated to have the most important impact. Even less exposed substituents provided hydrophobic force to the antigen-antibody interaction. Dislocated orientation of analyte functional groups could lead to steric hindrance and hydrophobic misleading of antibody recognition. This may happen even when the antigens contained the same substituent as the hapten. Frontier orbital energies also affect the reaction significantly. This study highlights of the power of CAMM-based analyses, providing insights into antibody recognition of small molecules.

Quantitative Structure-Activity Analysis of Triazines Immune Recognition Based on Immunoassay Data for Polyclonal and Monoclonal Antibodies

“…The immunoassay determination of triazines is much easier, less expensive, highly sensitive and rapid. Due to its selectivity and simplicity the immunoassay has been used to detect a wide variety of environmental pollutants including triazines [8][9][10].…”

“…Quantitative structure-activity relationship (QSAR) is widely used studying the immune recognition of diffferent classes of toxic food contaminants, veterinary drugs, including pesticides, etc [11][12][13][14]. The work by Yuan and co-authors reported about an immunoassay analysis of triazines, yet on a small set of 11 compounds [9]. QSAR is used for the analysis of immunoassays on quinolones and fluoroquinolones [15][16][17][18][19], organophosphorus pesticides [20][21], phenylurea herbicides [22], sulfonamides [23].…”

Stereospecific recognition and quantitative structure–activity relationship between antibodies and enantiomers: ofloxacin as a model hapten

“…12,13 The most widely used QSAR methods are traditional two-dimensional QSAR (2D-QSAR) based on the Hansch method and three-dimensional QSAR (3D-QSAR), such as comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). 13 Those approaches showed great power in cross-reactivity (CR) prediction 14,15 , explanation 3, 16, 17 , hapten design 18 and hapten-antibody recognition 2,3,19 . Although there were several QSAR studies carried out on antigen-antibody interaction studies, 13 recognition between chiral hapten and sterospecific antibody has not been seldom reported.…”

Aplicações de química teórica no estudo de materiais: métodos in silico para nanomateriais

“…142Garcia et al (2015). 143Yuan et al (2012),Mulyanto (2011), Hanasaki et al (2008,Carreño et al (2008),Mikulska et al (2011).…”