Submitted to: Analytica Chimica Acta
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/2/2009
Publication Date: 6/7/2009
Publication URL: http://hdl.handle.net/10113/36361
Citation: Xu, Z., Shen, Y., Beier, R.C., Yang, J., Lei, H., Wang, H., Sun, Y. 2009. Application of computer-assisted molecular modeling for immunoassay of low molecular weight food contaminants: A review. Analytica Chimica Acta. 647:125-136. Interpretive Summary: Immunoassay for low molecular weight food contaminants, such as pesticides, veterinary drugs, and mycotoxins is now a well-established technique that is rapid, reliable, and cost-effective. An immunoassay is similar to a pregnancy test, and uses specifically designed antibodies. Antibodies are substances that are produced by the immune system in response to foreign substances or antigens which enter the body. However, due to limited understanding of the fundamental aspects of immunoassay, such as the molecular structure of antibody and the intermolecular binding forces that come into play during antibody binding, the initial empirical method used to develop antibodies still primarily remains the method of choice. This paper reviews the use of computer-assisted molecular modeling (software methods used on a computer to calculate information about small molecules, and the larger proteins that interact with them) as a tool to help the scientist develop better antibodies and improve immunoassays.
Technical Abstract: Immunoassay for low molecular weight food contaminants, such as pesticides, veterinary drugs, and mycotoxins is now a well-established technique which meets the demands for a rapid, reliable, and cost-effective analytical method. However, due to limited understanding of the fundamental aspects of immunoassay, such as the molecular structure of antibody binding sites and epitopes, as well as the intermolecular binding forces that come into play, the initial empirical method used to develop antibodies still primarily remains the method of choice. Therefore, the development of immunochemical techniques, including specific-assays and group/class-specific assays, calls for new approaches to antibody design that will improve the affinity and specificity of the antibody by a more rapid and economic manner. Recently, computer-assisted molecular modeling (CAMM) has been demonstrated to be a useful tool to help the immunochemist develop assays and to direct improvements to important antibody features. CAMM is a tool that can provide insights into molecular structure and biological activity that are difficult or impossible to obtain in any other way. In this review, we briefly summarize applications of CAMM in immunoassay development, including assisting in hapten design, explaining cross-reactivity, modeling antibody-antigen interactions, and providing insights into the tertiary structure of a hapten during presentation to the immune system during antibody production.