Modelos teóricos simplificados aplicados no desenvolvimento de proteínas para diagnóstico e imunoterapia de alergia respiratória

Abstract

Blomia tropicalis family mites are prevalent in house dust and they are primarily responsible for allergic respiratory diseases in the world, generally in tropical and subtropical regions. In this study, we applied molecular dynamics simulations with simplified models and electrostatic calculations for the characterization of the recombinant Blomia tropicalis allergen protein group 5 (rBlo t 5). The objective was produce a new allergen with the same thermodynamic characteristic of Blomia tropicalis in their native form (rBlo t 5), therefore with immunological properties modified in order to promote the reduction of allergenicity by IgE and increased the immunogenicity response for use immunotherapy. It was performed structure-based model simulations only with the protein alpha carbons. Thermodynamic analysis showed that the native and the mutant Blo t 5 have similar thermalstability of ΔF = 2.2 kT. The charge-charge interaction by the new technique Tanford-Kirkwood Surface Accessibility – Monte Carlo (TKSA-MC) has been employed for the understanding of protein thermostability and modeling by means of optimization of the electrostatic interaction and it was applied in the proteins under study. The TKSA-MC results show an electrostatic interaction more favourable in the epitope region of mBlo T 5 with relation to rBlo t 5. These theoretical results corroborated with the experimental data, which shows that the modified allergen rBlo t 5 has a shift isotype to an increased antigenicity for the antibody IgG4, thus making suitable its application as potential candidate for immunotherapy studies with specific allergens.