Funding from the Department of Energy has allowed us to develop an expert system, MASIA, to quantitatively identify motifs and patterns of diversity in protein sequences. In addition we have developed computational approaches for protein fold recognition and homology modeling strategies. These computational methods were applied to several biochemical systems of high biomedical interests in collaborations with research groups at UTMB. With Drs. R.M. Goldblum and E.G. Brooks (Dept. of Pediatrics, UTMB) we developed 3D model structures of novel allergens Jun a 1 and Jun a 3 isolated from Mountain Cedar pollen. Allergenic epitopes of this protein, identified by IgE reactivity of tryptic peptides, were mapped to the surface of this model. The model structure has been used to guide site directed mutagenesis and peptide design in new therapeutic approaches.
There are some striking similarities among the known 3D structures of allergens, even when these do not share significant protein sequence identity. We have begun to assemble a 3D-database of allergen structures, which combines experimental results and our models for other known allergens. We will decompose the basic elements of IgE reactivity on Jun a 1 and Jun a 3 and seek relevant structural homologues in other allergens. These computational efforts should aid in designing new treatments for allergy that inhibit the process before interaction with mucosal basophils stimulates histamine release.