TITLE:
Searching for Novel Targets to Control Wheat Head Blight Disease—I-Protein Identification, 3D Modeling and Virtual Screening
AUTHORS:
Natália F. Martins, Emmanuel Bresso, Roberto C. Togawa, Martin Urban, John Antoniw, Bernard Maigret, Kim Hammond-Kosack
KEYWORDS:
Fusarium graminearum, Fungicide Development, 3D Protein Modeling, Target Selection
JOURNAL NAME:
Advances in Microbiology,
Vol.6 No.11,
September
14,
2016
ABSTRACT: Fusarium head blight (FHB) is a destructive disease of wheat and other cereals.
FHB occurs in Europe, North America and around the world causing significant
losses in production and endangers human and animal health. In this article, we
provide the strategic steps for the specific target selection for the
phytopathogen system wheat-Fusarium
graminearum. The economic impact of FHB leads to the need for innovation.
Currently used fungicides have been shown to be effective over the years, but recently
cereal infecting Fusaria have
developed resistance. Our work presents a new perspective on target selection
to allow the development of new fungicides. We developed an innovative approach
combining both genomic analysis and molecular modeling to increase the
discovery for new chemical compounds with both safety and low environmental
impact. Our protein targets selection revealed 13 candidates with high
specificity, essentiality and potentially assayable with a favorable
accessibility to drug activity. Among them, three proteins: trichodiene
synthase, endoglucanase-5 and ERG6 were selected for deeper structural analyses
to identify new putative fungicides. Overall, the bioinformatics filtering for
novel protein targets applied for agricultural purposes is a response to the demand
for chemical crop protection. The availability of the genome, secretome and
PHI-base allowed the enrichment of the search that combined experimental data in planta. The homology modeling and
molecular dynamics simulations allowed the acquisition of three robust and
stable conformers. From this step, approximately ten thousand compounds have
been virtually screened against three candidates. Forty-five top-ranked
compounds were selected from docking results as presenting better interactions
and energy at the binding pockets and no toxicity. These compounds may act as
inhibitors and lead to the development of new fungicides.