IN SILICO DESIGN OF HIGH-AFFINITY RECOMBINANT ANTIBODIES

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Currently there is a trend to move from small drug molecule therapy to use of biologics such as monoclonal antibodies (mAb). MAb therapy uses highly specific antibodies to bind to particular cells or proteins, in order to stimulate the immune system to destroy or neutralise those components that may be involved in disease progression. In a natural immune response, early antibodies bind with low affinity and are less specific about which antigen they bind to. As the immune response continues and there is long-term exposure to an antigen, the antibodies "mature", as a result of mutations in the binding regions of the antibodies. This leads to an increase or decrease in binding affinity. This provides a blueprint for the computational design of effective antibodies, with the advantage that we do not need to rely on purely random mutations but can be guided by our understanding of the interactions between biomolecules and antigens.In this project we will use a variety of biomolecular simulation techniques to study the binding process, and to design mutated structures to optimise the binding of the antibody to its antigen, whilst maintaining selectivity. The designed antibody structure will be produced recombinantly and tested experimentally, and if successful our strategy will yield new technology of immense impact. The industrial partner for this project will be able to utilise the technology in their portfolio of antibodies.