Modelagem e docking molecular da glutationa s-transferase epsilon 2 de aedes aegypti: possíveis implicações na resistência a inseticidas químicos.

Abstract

Glutathione S-transferases are a superfamily of enzymes involved in cell detoxification reactions in wide range of organisms. In mosquito there are at least six classes of GSTs In the epsilon class of this superfamily, AaGSTE2 (glutathione S-transferase epsilon 2 from Aedes aegypti) has been associated with resistance to various chemical insecticides. The indiscriminate use of these compounds to combat mosquitoes that transmit several diseases, such as dengue, ended up selecting a variety of resistant insects. The ability of these enzymes to evolve also contributed to the occurrence of this phenomenon. Considering that the function of an enzyme is closely related to its three-dimensional structure, bioinformatics tools such as homology modeling has been applied in the study of protein elucidation. Thus, due to the availability of the sequence of this enzyme in a database, the present work aimed to construct a model for AaGSTE2, by computational techniques, such as the homology modeling method. The reference sequence (template) used to construct the model was an epsilon Stransferase glutathione class of Anopheles gambiae for presenting 71% identity, the same was obtained in the PDB database. The model was built with the help of Swiss model software and validated through the PROCHECK program. With the help of GHECOM, a search of the amino acids that were participating in the GST catalytic site was also carried out. Then, with the model built, molecular docking was performed with DDT, Carbaryl and CDNB against GST in the AUTODOCK 1.5.6 program, to verify possible conjugations between the substrates and the enzyme. The results of modeling and molecular docking pointed a possible role of AaGSTE2 in insecticide resistance. Additionally, it can be conclude that the methodology used in the research may be useful in future studies to elucidate proteins. As it is also possible to perform molecular docking studies with other types of chemical insecticides with the model of the enzyme constructed.