Application of Computer-Assisted Molecular Modeling for Haptens of Interest in Food Safety Analyses

VARGAS JENTZSCH, PAUL; LAVECCHIA, MARTIN J.; GARRIDO, PATRICIA; RAMOS GUERRERO, LUIS; BRAVO, JUAN

Medellin

Workshop; Latin American Workshop in Structural Bioinformatics of Proteins; 2019

CABANA

Pyrrolizidine alkaloids (PAs) are secondary metabolites that are produced by some plant species. PAs are among the first natural carcinogens identified in plant products. Human, livestock, and wildlife can be exposed to PAs compounds as aresult of accidental consumption due to contamination of the food source. PAs determination is made mainly by methods based on liquid chromatography coupled to mass spectrometry (LC-MS). In general, the application of chromatographic techniques requires specialized facilities and highly trained technicians. On the other hand, Enzyme-Linked ImmunoSorbent Assay (ELISA) is a screening analysis that is used as a rapid, highly sensitive initial trial. For the development of those assays, haptens are required to obtain the antibodies used in ELISA test. Haptens are molecules that have similar structures to the analytes sought but join to a protein linker. The degree of similarity of the hapten with the analyte will determine the specificity of the test. In this sense, the use of computational tools based on the Density Functional Theory (DFT) for the analysis of the similarity between phytotoxins and their corresponding haptens is proposed. Moreover, the structural properties of selected haptens bounded to the carrier protein, albumin, to form the immunogen, was evaluated by molecular dynamics with molecular mechanics force fields. This computational strategy allows evaluating the possible hapten location concerning the carrier protein, taking also in consideration the in influence of a specific solvent and the effect of temperature. Finally, best choices of haptens, from a theoretical point of view, are recommended for the development of more eficient ELISA for PAs.