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. RM Goldblum and EG.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
allergies, that will inhibit the immunogenic process before interaction
of allergens with mucosal basophils stimulating histamine release.
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