Computationally Grafting An IgE Epitope Onto A Scaffold
AbstractDue to the increased hygienic life style of the developed world allergy is an increasing disease. Once allergy develops, sufferers are permanently trapped in a hyper immune response that makes them sensitive to innocuous substances. This paper discusses the strategy and protocol employed which designed proteins displaying a human IgE motif very close in proximity to the IgE’s FcεRI receptor binding site. The motif of interest was the FG motif and it was excised and grafted onto the protein scaffold 1YN3. The new structure (scaffold + motif) was fixed-backbone sequence designed around the motif to find an amino acid sequence that would fold to the designed structure correctly. Ten computationally designed proteins showed successful folding when simulated using the AbinitioRelax folding simulation and the IgE epitope was clearly displayed in its native three dimensional structure in all of them. Such a designed protein has the potential to be used as a pan anti-allergy vaccine by guiding the immune system towards developing antibodies against this strategic location on the body’s own IgE molecule, thus neutralising it and presumably permanently shutting down a major aspect of the Th2 immune pathway.