The use of monoclonal antibodies (mAbs) in research, diagnostics and therapeutics is ubiquitous, particularly because of their ability to simultaneously achieve high affinity and specificity. mAbs binding typically involves interactions between it and 5-8 amino acids in a specific spatial arrangement. These interactions at defined positions is what affords mAbs both high affinity and high specificity. Understanding these interactions would enable the rational design of mAbs with desired properties as opposed to current methods, which are primarily experimental. Unfortunately, because these interactions are quite complex, predictive modeling of mAb binding has continued to be a challenging problem, particularly when scaling to large numbers of mAbs and large numbers of potential targets or off-targets.
Researchers at The Biodesign Institute of Arizona State University have developed a novel bioinformatics tool to determine antigen and epitope targets of antibody binding. This method obtains a comprehensive relationship describing the binding of an antibody sample to any short linear sequence of amino acids. This relationship can then be used to determine the target of antibody binding in a particular protein, a whole proteome or group of proteomes. This would be particularly useful for characterizing the binding sites of antibody samples as well as determining potential off target sites.
This technology is able to generate comprehensive models which are predictive of highly specific molecular recognition to identify antibodies which can be used in a number of applications.
Potential Applications
- Mapping binding sequences of antibodies
- Selecting highly specific antibodies for therapeutic, diagnostic or research applications
Benefits and Advantages
- Rapidly provides highly specific sequence binding information without any prior knowledge of the binding of the antibodies
- Particularly true for antibodies that binding linear epitopes
- Statistically high accuracy
- Simple and rapid test that requires only small amounts of sample
- Works for any antibody that binds to sequences of amino acids
- Works with monoclonal and polyclonal antibodies, as well as blood or serum samples
- Able to predict sequences that are likely to bind strongly and thus are epitopes, mimotopes or just off target binding sequences
- Off-target binding is particularly important with regard to therapeutic mAbs
- Can determine the target of antibody binding in a particular protein, a whole proteome or group of proteomes
- A comprehensive model can be created from sparse sampling without a priori bias in the sequences used to train the model and no bias in the predictions
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