Title:In silico Characterization of an Initiation Factor 2 Kinase of Black Fungi:
A Potential Drug Target for Mycosis
Volume: 13
Issue: 2
Author(s): Cláudia Barbosa Assunção, Edgar Lacerda de Aguiar*, Miguel A. Chávez-Fumagalli, Emanuelle Rutren La Santrer, Sandro Renato Dias, Thiago de Souza Rodrigues and Rachel Basques Caligiorne
Affiliation:
- Post-graduate Program in Modelagem Matemática Computacional, Centro, Federal de Educação Tecnológica
de Minas Gerais - CEFET-MG, MG, Brazil
Keywords:
eIF-2 Kinase, drug target prediction, black fungi, mycoses, antifungal agents, network.
Abstract: Fungi infections are responsible for more than 1.6 million deaths per year worldwide.
Treatment is time-consuming, compromising the kidney and liver functions. In silico analyses
have facilitated the discovery of new drugs that may present fewer side effects. In this connection,
kinases that phosphorylate the translation initiation factor eIF-2 are candidate proteins for potent
new drugs, which have been recognized as important in maintaining protein synthesis. Substances
that interfere with the phosphorylation of the eIF2α factor may be the way to inhibit the production
of proteins and accelerate the fungi's death. To determine whether this enzyme can be used as
a new drug target, this study aimed to perform In silico functional annotation and characterization
of eIF2 factor kinase´s three-dimensional structure from three species of black fungi. In addition,
inhibitors that could interact and bind to the active site of the enzyme were explored. The hypothetical
protein was submitted to the databases and bioinformatics tools for its characterization, whose
analysis of protein-protein interactions was modeled and inhibitors anchored. Protein interaction
analysis linked the kinases with other molecules in protein translation and ribosome recycling.
However, centrality analysis showed only one kinase as a possible drug target. The inhibitors
showed coupling with the active site of protein kinases, and these results indicate a possible blockade
of the enzymatic function that can accelerate the response to the drugs. This study demonstrates
that biochemical characterization and In silico validation studies of potential drugs can be
more efficient and yield faster results
